bluuebunny/crossref_metadata_2025_split huggingface dataset:
MCC950, a selective NLPR3 inflammasome inhibitor, improves neurologic function and survival after cardiac arrest and resuscitation
Authors: Jiang Maorong , Li Ran , Lyu Jingjun , Li Xuan , Wang Wei , Wang Zhuoran , Sheng Huaxin , Zhang Weiguo , Karhausen Jörn , Yang Wei 
Published: August 2020

AbstractBackgroundCardiac arrest (CA) is associated with high morbidity and mortality, even after spontaneous circulation is re-established. This dire situation is partly due to post-CA syndrome for which no specific and effective intervention is available. One key component of post-CA syndrome is sterile inflammation, which affects various organs including the brain. A major effector of sterile inflammation is activated NLRP3 inflammasome, which leads to increased release of interleukin (IL)-1β. However, how NLRP3 inflammasome impacts neuroinflammation and neurologic outcome after CA is largely undefined.MethodsMice were subjected to a potassium-based murine CA and cardiopulmonary resuscitation (CPR) model. MCC950 was used to suppress activation of NLRP3 inflammasome after CA/CPR. Levels of protein and mRNA were examined by Western blotting and quantitative PCR, respectively. Immunologic changes were assessed by measuring cytokine expression and immune cell compositions. CA outcomes, including neurologic deficits, bacterial load in the lung, and survival rate, were evaluated.ResultsUsing our CA/CPR model, we found that NLRP3 inflammasome was activated in the post-CA brain, and that pro-inflammatory cytokine levels, including IL-1β, were increased. After treatment with MCC950, a potent and selective NLRP3 inflammasome inhibitor, mice exhibited improved functional recovery and survival rate during the 14-day observational period after CA/CPR. In line with these findings, IL-1β mRNA levels in the post-CA brain were significantly suppressed after MCC950 treatment. Interestingly, we also found that in MCC950- vs. vehicle-treated CA mice, immune homeostasis in the spleen was better preserved and bacterial load in the lung was significantly reduced.ConclusionsOur data demonstrate that activation of NLRP3 inflammasome could be a key event shaping the post-CA immuno- and neuro-pathology, and identify this pathway as a unique and promising therapeutic target to improve outcomes after CA/CPR.
Influence of the amino-terminal sequence on the structure and function of HIV integrase
Authors: Eilers Grant , Gupta Kushol , Allen Audrey , Zhou Jeffrey , Hwang Young , Cory Michael B. , Bushman Frederic D. , Van Duyne Gregory 
Published: August 2020

Abstract
Background
Antiretroviral therapy (ART) can mitigate the morbidity and mortality caused by the human immunodeficiency virus (HIV). Successful development of ART can be accelerated by accurate structural and biochemical data on targets and their responses to inhibitors. One important ART target, HIV integrase (IN), has historically been studied in vitro in a modified form adapted to bacterial overexpression, with a methionine or a longer fusion protein sequence at the N-terminus. In contrast, IN present in viral particles is produced by proteolytic cleavage of the Pol polyprotein, which leaves a phenylalanine at the N-terminus (IN 1F). Inspection of available structures suggested that added residues on the N-terminus might disrupt proper protein folding and formation of multimeric complexes.

Results
We purified HIV-1 IN 1F1–212 and solved its structure at 2.4 Å resolution, which showed extension of an N-terminal helix compared to the published structure of IN1–212. Full-length IN 1F showed increased in vitro catalytic activity in assays of coupled joining of the two viral DNA ends compared to two IN variants containing additional N-terminal residues. IN 1F was also altered in its sensitivity to inhibitors, showing decreased sensitivity to the strand-transfer inhibitor raltegravir and increased sensitivity to allosteric integrase inhibitors. In solution, IN 1F exists as monomers and dimers, in contrast to other IN preparations which exist as higher-order oligomers.

Conclusions
The structural, biochemical, and biophysical characterization of IN 1F reveals the conformation of the native HIV-1 IN N-terminus and accompanying unique biochemical and biophysical properties. IN 1F thus represents an improved reagent for use in integration reactions in vitro and the development of antiretroviral agents.
What can be done to reduce the prevalence of teen pregnancy in rural Eastern Uganda?: multi-stakeholder perceptions
Authors: Nabugoomu Josephine , Seruwagi Gloria K. , Hanning Rhona 
Published: August 2020

Abstract
Introduction
The teenage pregnancy rate of 25% in Uganda is worrying though it may seem low compared to 28% in Sub-Saharan countries and West and Central Africa. Young mothers in Uganda risk poor maternal and child health, being isolated, attempting unsafe abortions, failure to continue with school, and poverty. This paper describes perceptions and recommendations of young mothers, family and community members on why the high rate of teenage pregnancies in Uganda and how these can be reduced.

Methods
This qualitative research was conducted from March to May 2016 in six communities within Budondo sub-county (Jinja district), Eastern Uganda. In-depth oral interviews were conducted with 101 purposively sampled adolescent mothers, family members, and workers of government and non-government organizations. Thematic analysis framed around levels of influence within a social cognitive framework was conducted using Atlas-ti (version 7.5.4).

Results
Perceived determinants of teenage pregnancies include: lack of life and social survival skills, lack of knowledge on how to avoid pregnancy, low acceptance/use of contraceptives, neglect by parents, sexual abuse, pressure to contribute to family welfare through early marriage or sexual transactions, lack of community responsibility, media influence, peer pressure, cultural beliefs that promote early marriage/childbearing and lack of role models. Other contributing factors include drug use among boys, poverty, late work hours, long travel distances, e.g., to school, and unsupervised locations like sugarcane plantation thickets. Recommendations participants offered include: sensitization seminars and counselling for parents and girls, closing pornography outlets that accept entrance of minors, using the law to punish rapists, involvement of the President to campaign against early pregnancies, school dismissal before dark, locally accessible schools and job creation for parents to earn money to support the girls financially. Areas for capacity building are: training teachers and community members in transferring empowerment and vocational skills to girls, and construction of homes with separate rooms to support parents’ privacy.

Conclusion
The factors associated with adolescent pregnancy in Uganda fall under individual, economic, social and physical environmental determinants. Recommendations spanning family, community and government involvement can ultimately empower girls, their families and community members, and support collective action to reduce teenage pregnancies.
Home-field advantage: native gecko exhibits improved exertion capacity and locomotor ability in structurally complex environments relative to its invasive counterpart
Authors: Garner Austin M. , Pamfilie Alexandra M. , Hamad E. J. , Kindig Rachael , Taylor Joshua T. , Unsworth Colleen K. , Niewiarowski Peter H. 
Published: August 2020

Abstract
Background
Invasive species are of substantial concern because they may threaten ecosystem stability and biodiversity worldwide. Not surprisingly, studies examining the drivers of biological invasion have increased in number over the past few decades in an effort to curtail invasive species success by way of informing management decisions. The common house gecko, Hemidactylus frenatus, has successfully invaded the Pacific islands where it appears to thrive in and dominate non-natural habitats offering high food availability (i.e., well-lit human dwellings) compared to native geckos. Previous work demonstrated that H. frenatus can outperform the native gecko, Lepidodactylus lugubris, in terms of maximal sprint speed on relatively simple planar surfaces (e.g., building walls). Lepidodactylus lugubris and other native geckos, however, may have superior locomotor performance in three-dimensional, structurally complex habitats.

Results
Here we compared the locomotor behaviour and exertion capacity of the native gecko, Gehyra oceanica, and the invasive gecko, Hemidactylus frenatus, on the island of Mo’orea, French Polynesia, on fabricated structures simulating structurally complex substrates. We found that the native gecko exhibits improved locomotor performance compared to the invasive gecko on structurally complex substrates. We also completed encounter surveys to document free-ranging habitat use and behaviour of these two species. We discovered that H. frenatus were more common in natural habitats than previously observed and used similar substrates as G. oceanica, although G. oceanica appeared to use substrates with greater perch heights (i.e., trees).

Conclusions
Our findings revealed that locomotor performance in complex environments may contribute to the previously observed habitat segregation between native and invasive Pacific island geckos. Furthermore, our locomotor and habitat use data are consistent with the hypothesis that G. oceanica may be resistant to invasion of H. frenatus in natural environments. Our study calls for more detailed ecophysiological and ecomorphological studies of both native and invasive Pacific gecko species.
Metastatic colon cancer of the small intestine diagnosed using genetic analysis: a case report
Authors: Matsuo Mikiko , Hatano Yuichiro , Imaizumi Yuko , Kuroda Takahiro , Arai Toshinori , Tomita Hiroyuki , Matsuhashi Nobuhisa , Yoshida Kazuhiro , Hara Akira 
Published: August 2020

Abstract
Background
Intestinal-type adenocarcinoma is widely detected in the gastrointestinal tract, head and neck, lower respiratory and urinary systems. Determining the nature (monoclonal or multicentric) of the intestinal adenocarcinoma is sometimes a diagnostic challenge owing to its occurrence at various locations of the body, especially in the lower gastrointestinal tract. Herein, we successfully diagnosed metastatic colon cancer in the small intestine using tumor protein 53 gene (TP53) mutation analysis.

Case presentation
An 83-year-old woman presented with severe abdominal pain and nausea at the emergency department of the hospital. Her history included surgery and adjuvant chemotherapy for colon and breast cancers. Abdominal computed tomography revealed small intestinal dilation, which was associated with the mural nodule detected on fluorodeoxyglucose positron emission tomography. Laparoscopy-assisted small bowel resection was performed based on the diagnosis of small bowel obstruction, probably due to recurrence of the colon or breast cancer. Macroscopically, an ulcerated tumor was present in the resected small intestine. Histologically, the cancer cells showed infiltrative growth of colonic dysplastic glands, whose non-specific finding made it difficult to determine the relationship with past colon cancers. Retrospective pathological examination confirmed that the previous breast and colon carcinomas were primary cancers. Immunohistochemical analysis revealed that the small intestinal and colon cancer cells showed diffuse positive tumor protein 53 (p53) expression. However, the breast cancer cells showed only weakly positive p53 expression. In addition, TP53 mutational analysis detected an identical missense mutation (p.T211I) between the two intestinal cancers. Moreover, further molecular genetic work-up revealed that both small intestinal and colon adenocarcinomas harbored an identical missense mutation (p.G12D) of KRAS gene. In conclusion, the small intestinal cancer in this case was identified as a metastatic adenocarcinoma arising from a past colon cancer.

Conclusions
Genetic analyses help in clarifying the identity of the cells in multiple cancer cases. In morphologically indeterminate cases, molecular analysis of common cancer-related genes can be useful for a precise and reproducible diagnosis.
Some notes on the use, concept and socio-political framing of ‘stigma’ focusing on an opioid-related public health crisis
Authors: Fischer Benedikt 
Published: August 2020

AbstractCanada has been home to a longstanding public health crisis related to opioids, including an extensive mortality and morbidity toll in the face of substantive intervention gaps. Recently (2019), two extensive reports from preeminent federal authorities – the Chief Public Health Officer and the Mental Health Commission of Canada – have been tabled with detailed, core focus on the phenomenon of ‘stigma’ and its impacts on substance/opioid use and harms. The reports present extensive descriptions of the nature and effects, as well as a multitude of prescriptions for remedial measures and actions to “stop the cycle of stigma”. Closer reading of the documents, however, suggests substantial conceptual and empirical limitations in the characterization of the – multi-faceted and challenging – nature and workings of ‘stigma’ as a socio-political, structural or individual process or force, specifically as it applies to and negatively affects substance use and related outcomes, primarily the wellbeing of substance users. Concretely, it is unclear how the remedial actions proposed will materially alleviate stigma process and impacts, especially given apparent gaps in the issues examined, including essential strategies – for example, reform of drug user criminalization as a fundamental element and driver of structural stigma - for action that directly relate to the jurisdictions and privileged mandates of the report sources themselves as health and policy leaders. The commentary provides some concrete while subjective notes and observations on the dynamics of stigma as applies to and framed for substance/opioid use, as well as strategies and measures necessary to both tangibly address the material health and wellbeing of substance users, and related forces of stigma, in the distinct context of the opioid crisis in Canada.
Analysis of the response time to involved-field radiotherapy in primary gastrointestinal low-grade B-cell lymphoma
Authors: Choi Kyu Hye , Lee Han Hee , Jung Seung-Eun , Park Kyung-Sin , O Joo-Hyun , Jeon Young-Woo , Choi Byung-Ock , Cho Seok-Goo 
Published: August 2020

Abstract
Background
Early-stage primary gastrointestinal (GI) low-grade B-cell lymphoma shows good therapeutic response to primary radiotherapy. However, there is no clear guideline for the evaluation of response to radiation therapy currently. The aim of this study was to analyze the relationship between the best response time and the clinical course after radiotherapy.

Methods
Patients who underwent radiotherapy for treatment of primary GI low-grade B-cell lymphoma from September 2007 to December 2018 at Seoul St. Mary’s Hospital were included. Early responders were defined by best response within 6 months after radiotherapy, and delayed responders after 6 months. Clinical and pathological factors associated with delayed response and survival analyses were performed to investigate the recurrence and survival during follow-up.

Results
A total of 43 patients were evaluated and the number of gastric mucosa-associated lymphoid tissue and duodenal follicular lymphoma was 36 and 7, respectively. All of 43 patients showed complete remission to radiotherapy and the best response time after radiotherapy was a median of 3 months. There were 8 delayed responders with a median duration of 8.9 months. Early and delayed responders were characterized by a significant difference in depth of invasion beyond the mucosal layer.

Conclusions
Delayed responders did not show differences in oncological outcomes compared with early responders. They were allowed to watch and wait for an additional 6 to 12 months without further treatment.
Mid-term follow-up after aortic valve replacement with the Carpentier Edwards Magna Ease prosthesis
Authors: Rajab Taufiek K. , Ali Jason M. , Hernández-Sánchez Jules , Mackie Jennifer , Grimaudo Vincenzo , Sinichino Silvia , Mills Christine , Rana Bushra , Dunning John , Abu-Omar Yasir 
Published: August 2020

Abstract
Background
Approximately 250,000 heart valve operations are performed annually worldwide. An intensive research and development effort has led to progressively more advanced heart valve prostheses. The Carpentier-Edwards Perimount Magna Ease (CEPME) prosthesis represents the latest iteration of the Edwards Perimount series of aortic tissue valves. The current study aims to evaluate the midterm performance of this bioprosthesis.

Methods
Five hundred and eighteen patients with aortic stenosis underwent aortic valve replacement with the CEPME valve at Papworth Hospital between August 2008 and November 2011. After a minimum of 3 years from the index operation, eligible patients were retrospectively and consecutively recruited to participate. Recruitment was closed after 100 eligible patients had completed all study assessments. Investigations at follow-up included echocardiography, and NYHA status. Primary endpoints included valve performance measures.

Results
The mean age was 72 years, 64% were male and median follow-up was 5.1 years. NYHA status had improved in 66% of patients. The average postoperative peak and mean pressure gradients decreased by 51.2 mmHg (64.5%) and 31.8 mmHg (59.4%), with a significant improvement in NYHA status. The frequency of moderate aortic regurgitation was 3%. There was no evidence for structural valve deterioration.

Conclusions
The CEPME has excellent mid-term durability. Its use effectively improves haemodynamics and functional capacity.
Congenital intrathoracic accessory spleen is a very rare trick of nature: a case report
Authors: Suraju Mohammed O. , Peyton Nicole , Mooers Brian , Jensen Chris , Shilyansky Joel 
Published: August 2020

Abstract
Background
Congenital intrathoracic accessory spleen (CIAS) refers to a developmental anomaly resulting in the presence of splenic tissue within the chest. The differential diagnoses for the resulting mass are pulmonary malformations, or lesions with malignant potential. To our knowledge, only four cases of presumed CIAS have been described in literature to date, and no cases were reported in the United States.

Case presentation
We report on a 14-year-old Caucasian female with a left chest mass discovered incidentally on a CT scan performed following an all-terrain vehicle accident. Following resection, the mass was diagnosed as a CIAS.

Conclusions
From our review of literature, we found that CIAS can pose a diagnostic dilemma as it is rare, difficult to distinguish from pulmonary sequestration, or malignancy, and biopsy is often inconclusive. Resection is required to rule out malignancy and determine the diagnosis. Pediatric thoracic surgeons should consider CIAS in their differential for an intrathoracic mass with an inconclusive biopsy.
A contemporary approach to a young female patient with Loeys-Dietz syndrome and an uncomplicated type B aortic dissection: a case report
Authors: Prodanov Petko , Linkova Hana , Petr Robert , Fojt Richard , Motovska Zuzana , Knot Jiri , Rohac Filip , Koznar Boris , Majid Mariwan , Widimsky Petr , Kacer Petr 
Published: August 2020

Abstract
Background
Aortic dissection is a relatively uncommon, but often catastrophic disease that requires early and accurate diagnosis. It often presents in patients with congenital connective tissue disorders. The current aortic surgical techniques are related with serious early and late complications. This case report emphasizes the importance of early diagnosis of aortic root dilatation and the risk of dissection, especially in patients with congenital connective tissue disorders. We present an alternative, contemporary and multidisciplinary approach based on the present state of knowledge.

Case presentation
We present a rare case of a young female patient with Loeys-Dietz syndrome who was admitted with an uncomplicated aortic dissection (Stanford type B / DeBakey type III) and a dilated aortic root. After a period of close surveillance and extensive vascular imaging, thoracic endovascular aortic repair was deemed to be technically not possible. Medical treatment was optimized and our patient successfully underwent a personalised external aortic root support procedure (PEARS) as a contemporary alternative to existing aortic root surgical techniques.

Conclusions
This case highlights the importance of interdisciplinary approach, close follow-up and multimodality imaging. The decision to intervene in a chronic type B aortic dissection is still challenging and should be made in experienced centers by an interdisciplinary team. However, if an acute complication occurs, thoracic endovascular aortic repair TEVAR is the method of choice. In all cases optimal medical treatment is important. There is increasing evidence that personalized external aortic root support procedure PEARS is effective in stabilizing the aortic root and preventing its dilatation and dissection not only in patients with Marfan syndrome, but also in other cases of aortic root dilation of other etiologies. Moreover, many publications have reported the additional benefit of reduction or even eradication of aortic regurgitation by improving coaptation of the aortic valve leaflets in dilated aortas.
Providing high-quality care remotely to patients with rare bone diseases during COVID-19 pandemic
Authors: Brizola E. , Adami G. , Baroncelli G. I. , Bedeschi M. F. , Berardi P. , Boero S. , Brandi M. L. , Casareto L. , Castagnola E. , Fraschini P. , Gatti D. , Giannini S. , Gonfiantini M. V. , Landoni V. , Magrelli A. , Mantovani G. , Michelis M. B. , Nasto L. A. , Panzeri L. , Pianigiani E. , Scopinaro A. , Trespidi L. , Vianello A. , Zampino G. , Sangiorgi L. 
Published: August 2020

AbstractDuring the COVID-19 outbreak, the European Reference Network on Rare Bone Diseases (ERN BOND) coordination team and Italian rare bone diseases healthcare professionals created the “COVID-19 Helpline for Rare Bone Diseases” in an attempt to provide high-quality information and expertise on rare bone diseases remotely to patients and healthcare professionals. The present position statement describes the key characteristics of the Helpline initiative, along with the main aspects and topics that recurrently emerged as central for rare bone diseases patients and professionals. The main topics highlighted are general recommendations, pulmonary complications, drug treatment, trauma, pregnancy, children and elderly people, and patient associations role. The successful experience of the “COVID-19 Helpline for Rare Bone Diseases” launched in Italy could serve as a primer of gold-standard remote care for rare bone diseases for the other European countries and globally. Furthermore, similar COVID-19 helplines could be considered and applied for other rare diseases in order to implement remote patients’ care.