bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical, genomics and networking analyses of a high-altitude native American Ecuadorian patient with congenital insensitivity to pain with anhidrosis: a case report
Authors: López-Cortés Andrés , Zambrano Ana Karina , Guevara-Ramírez Patricia , Echeverría Byron Albuja , Guerrero Santiago , Cabascango Eliana , Pérez-Villa Andy , Armendáriz-Castillo Isaac , García-Cárdenas Jennyfer M. , Yumiceba Verónica , Pérez-M Gabriela , Leone Paola E. , Paz-y-Miño César 
Published: August 2020

Abstract
Background
Congenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare autosomal recessive disorder characterized by insensitivity to pain, inability to sweat and intellectual disability. CIPA is caused by mutations in the neurotrophic tyrosine kinase receptor type 1 gene (NTRK1) that encodes the high-affinity receptor of nerve growth factor (NGF).

Case presentation
Here, we present clinical and molecular findings in a 9-year-old girl with CIPA. The high-altitude indigenous Ecuadorian patient presented several health problems such as anhidrosis, bone fractures, self-mutilation, osteochondroma, intellectual disability and Riga-Fede disease. After the mutational analysis of NTRK1, the patient showed a clearly autosomal recessive inheritance pattern with the pathogenic mutation rs763758904 (Arg602*) and the second missense mutation rs80356677 (Asp674Tyr). Additionally, the genomic analysis showed 69 pathogenic and/or likely pathogenic variants in 46 genes possibly related to phenotypic heterogeneity, including the rs324420 variant in the FAAH gene. The gene ontology enrichment analysis showed 28 mutated genes involved in several biological processes. As a novel contribution, the protein-protein interaction network analysis showed that NTRK1, SPTBN2 and GRM6 interact with several proteins of the pain matrix involved in the response to stimulus and nervous system development.

Conclusions
This is the first study that associates clinical, genomics and networking analyses in a Native American patient with consanguinity background in order to better understand CIPA pathogenesis.
Stable high frequencies of sulfadoxine–pyrimethamine resistance associated mutations and absence of K13 mutations in Plasmodium falciparum 3 and 4 years after the introduction of artesunate plus sulfadoxine–pyrimethamine in Ujjain, Madhya Pradesh, India
Authors: Pathak Ashish , Mårtensson Andreas , Gawariker Sudhir , Sharma Ashish , Diwan Vishal , Purohit Manju , Ursing Johan 
Published: August 2020

Abstract
Background
Artesunate plus sulfadoxine–pyrimethamine (ASP) is first-line treatment for uncomplicated Plasmodium falciparum malaria in most of India, except for six North-eastern provinces where treatment failure rates were high. In Ujjain, central India, the frequency of mutations associated with increased drug tolerance, but not overt resistance to sulfadoxine and pyrimethamine were 9% and > 80%, respectively, in 2009 and 2010, just prior to the introduction of ASP. The frequency of drug resistance associated mutations in Ujjain in 2015–2016 after 3–4 years of ASP use, are reported.

Methods
Blood samples from patients with P. falciparum mono-infection verified by microscopy were collected on filter-paper at all nine major pathology laboratories in Ujjain city. Codons pfdhfr 16–185, pfdhps 436–632 and K13 407–689 were identified by sequencing. Pfcrt K76T and pfmdr1 N86Y were identified by restriction fragment length polymorphism.

Results
Sulfadoxine–pyrimethamine resistance-associated pfdhfr 108 N and 59R alleles were found in 100/104 (96%) and 87/91 (96%) samples, respectively. Pfdhps 437G was found in 10/105 (10%) samples. Double mutant pfdhfr 59R + 108 N were found in 75/81 (93%) samples. Triple mutant pfdhfr 59R + 108 N and pfdhps 437G were found in 6/78 (8%) samples. Chloroquine-resistance-associated pfcrt 76T was found in 102/102 (100%). Pfmdr1 N86 and 86Y were identified in 83/115 (72%) and 32/115 (28%) samples, respectively.

Conclusion
The frequency of P. falciparum with reduced susceptibility to sulfadoxine–pyrimethamine remained high, but did not appear to have increased significantly since the introduction of ASP. No polymorphisms in K13 associated with decreased artemisinin susceptibility were found. ASP probably remained effective, supporting continued ASP use.
Assessment of molecular markers of anti-malarial drug resistance among children participating in a therapeutic efficacy study in western Kenya
Authors: Chebore Winnie , Zhou Zhiyong , Westercamp Nelli , Otieno Kephas , Shi Ya Ping , Sergent Sheila B. , Rondini Kelsey Anne , Svigel Samaly Souza , Guyah Benard , Udhayakumar Venkatachalam , Halsey Eric S. , Samuels Aaron M. , Kariuki Simon 
Published: August 2020

AbstractBackgroundAnti-malarial drug resistance remains a major threat to global malaria control efforts. In Africa,Plasmodium falciparumremains susceptible to artemisinin-based combination therapy (ACT), but the emergence of resistant parasites in multiple countries in Southeast Asia and concerns over emergence and/or spread of resistant parasites in Africa warrants continuous monitoring. The World Health Organization recommends that surveillance for molecular markers of resistance be included within therapeutic efficacy studies (TES). The current study assessed molecular markers associated with resistance to Artemether−lumefantrine (AL) and Dihydroartemisinin−piperaquine (DP) from samples collected from children aged 6–59 months enrolled in a TES conducted in Siaya County, western Kenya from 2016 to 2017.MethodsThree hundred and twenty-three samples collected pre-treatment (day-0) and 110 samples collected at the day of recurrent parasitaemia (up to day 42) were tested for the presence of drug resistance markers in thePfk13propeller domain, and thePfmdr1andPfcrtgenes by Sanger sequencing. Additionally, thePfpm2gene copy number was assessed by real-time polymerase chain reaction.ResultsNo mutations previously associated with artemisinin resistance were detected in thePfk13propeller region. However, other non-synonymous mutations in thePfk13propeller region were detected. The most common mutation found on day-0 and at day of recurrence in thePfmdr1multidrug resistance marker was at codon 184F. Very few mutations were found in thePfcrtmarker (< 5%). Within the DP arm, all recrudescent cases (8 sample pairs) that were tested forPfpm2gene copy number had a single gene copy. None of the associations between observed mutations and treatment outcomes were statistically significant.ConclusionThe results indicate absence ofPfk13mutations associated with parasite resistance to artemisinin in this area and a very high proportion of wild-type parasites forPfcrt. Although the frequency ofPfmdr1184Fmutations was high in these samples, the association with treatment failure did not reach statistical significance. As the spread of artemisinin-resistant parasites remains a possibility, continued monitoring for molecular markers of ACT resistance is needed to complement clinical data to inform treatment policy in Kenya and other malaria-endemic regions.
Effectiveness of the innovative 1,7-malaria reactive community-based testing and response (1, 7-mRCTR) approach on malaria burden reduction in Southeastern Tanzania
Authors: Mlacha Yeromin P. , Wang Duoquan , Chaki Prosper P. , Gavana Tegemeo , Zhou Zhengbin , Michael Mihayo G. , Khatib Rashid , Chila Godlove , Msuya Hajirani M. , Chaki Exavery , Makungu Christina , Lin Kangming , Tambo Ernest , Rumisha Susan F. , Mkude Sigsbert , Mahende Muhidin K. , Chacky Frank , Vounatsou Penelope , Tanner Marcel , Masanja Honorati , Aregawi Maru , Hertzmark Ellen , Xiao Ning , Abdulla Salim , Zhou Xiao-Nong 
Published: August 2020

AbstractBackgroundIn 2015, a China-UK-Tanzania tripartite pilot project was implemented in southeastern Tanzania to explore a new model for reducing malaria burden and possibly scaling-out the approach into other malaria-endemic countries. The 1,7-malaria Reactive Community-based Testing and Response (1,7-mRCTR) which is a locally-tailored approach for reporting febrile malaria cases in endemic villages was developed to stop transmission andPlasmodiumlife-cycle. The (1,7-mRCTR) utilizes existing health facility data and locally trained community health workers to conduct community-level testing and treatment.MethodsThe pilot project was implemented from September 2015 to June 2018 in Rufiji District, southern Tanzania. The study took place in four wards, two with low incidence and two with a higher incidence. One ward of each type was selected for each of the control and intervention arms. The control wards implemented the existing Ministry of Health programmes. The 1,7-mRCTR activities implemented in the intervention arm included community testing and treatment of malaria infection. Malaria case-to-suspect ratios at health facilities (HF) were aggregated by villages, weekly to identify the village with the highest ratio. Community-based mobile test stations (cMTS) were used for conducting mass testing and treatment. Baseline (pre) and endline (post) household surveys were done in the control and intervention wards to assess the change in malaria prevalence measured by the interaction term of ‘time’ (post vs pre) and arm in a logistic model. A secondary analysis also studied the malaria incidence reported at the HFs during the intervention.ResultsOverall the 85 rounds of 1,7-mRCTR conducted in the intervention wards significantly reduced the odds of malaria infection by 66% (adjusted OR 0.34, 95% CI 0.26,0.44, p < 0001) beyond the effect of the standard programmes. Malaria prevalence in the intervention wards declined by 81% (from 26% (95% CI 23.7, 7.8), at baseline to 4.9% (95% CI 4.0, 5.9) at endline). In villages receiving the 1,7-mRCTR, the short-term case ratio decreased by over 15.7% (95% CI − 33, 6) compared to baseline.ConclusionThe 1,7-mRCTR approach significantly reduced the malaria burden in the areas of high transmission in rural southern Tanzania. This locally tailored approach could accelerate malaria control and elimination efforts. The results provide the impetus for further evaluation of the effectiveness and scaling up of this approach in other high malaria burden countries in Africa, including Tanzania.
A moderate-carbohydrate diet with plant protein is inversely associated with cardiovascular risk factors: the Korea National Health and Nutrition Examination Survey 2013–2017
Authors: Ha Kyungho , Nam Kisun , Song YoonJu 
Published: August 2020

Abstract
Background
Because a moderate-carbohydrate diet reportedly has minimal risks, the substitution of carbohydrate for protein has been emphasized. Few studies have explored the effect of moderate-carbohydrate diets with higher protein intake in Asians, who typically consume a high-carbohydrate low-fat diet. Therefore, this study evaluated the associations of moderate- versus high- carbohydrate diets with cardiovascular risk factors among Korean adults by protein source.

Methods
This study included 7965 adults (3196 men, 4769 women) aged ≥ 19 years who participated in the 2013–2017 Korea National Health and Nutrition Examination Survey. Dietary intake was assessed by a 24-h recall method and four types of diet were defined: a moderate-carbohydrate diet with plant protein (MCP) or animal protein (MCA) and a high-carbohydrate diet with plant protein (HCP) or animal protein (HCA).

Results
Compared with the MCP group, men in the other three groups had significantly higher odds ratios (ORs) for elevated total cholesterol, reduced high-density lipoprotein (HDL)-cholesterol, and metabolic syndrome. Among women, only the HCP group had an increased OR for reduced HDL-cholesterol, compared with the MCP group. Similar associations were observed in younger adults (19–49 years). In addition, younger adults in the MCA group exhibited higher ORs for elevated triglycerides in men and elevated total cholesterol in women, compared with those in the MCP group.

Conclusions
A moderate-carbohydrate diet with a high intake of plant protein was inversely associated with cardiovascular risk factors, especially among younger Korean adults. Further intervention studies are required to confirm this relationship and develop the optimal diet for cardiovascular health in the Korean population.
Atherogenic index of plasma predicts cerebrovascular accident occurrence in antineutrophil cytoplasmic antibody-associated vasculitis
Authors: Ahn Sung Soo , Lee Lucy Eunju , Pyo Jung Yoon , Song Jason Jungsik , Park Yong-Beom , Lee Sang-Won 
Published: August 2020

Abstract
Background
To investigate whether atherogenic index of plasma (AIP) at diagnosis is associated with the occurrence of cerebrovascular accident (CVA) or coronary artery disease (CAD) in antineutrophil cytoplasmic antibody-associated vasculitis (AAV).

Methods
The medical records of 167 AAV patients on initial diagnosis was reviewed, and 300 healthy controls were included. AIP was calculated using the following equation: AIP = Log (triglyceride [mg/dL] / high-density lipoprotein cholesterol [mg/dL]). AAV patients were divided into two groups according to the AIP cut-off of 0.11. The event of stroke, transient ischemic attack, and cerebral hemorrhage was recorded as CVA, and CAD events consisted of either myocardial infarction and angina pectoris. CVA- and CAD- free survival rate between those with AIP ≥ 0.11 and < 0.11 were compared by the Kaplan-Meier analysis, and Cox hazard analysis was conducted to identify predictors of CVA.

Results
The median age of AAV patients were 59.0 years, and 54 (32.3%) patients were male. One-hundred and fifteen (68.9%) patients had AIP < 0.11 and 52 (31.1%) had AIP ≥ 0.11. The mean Birmingham vasculitis activity score in AAV patients with AIP < 0.11 was lower than that seen in patients with AIP ≥ 0.11 (12.0 vs. 14.0, P = 0.041). AAV patients had a significantly higher AIP compared to controls (mean − 0.01 vs. -0.10, P < 0.001). During follow-up, the occurrence of CVA and CAD was observed in 16 (9.6%) and 14 (8.4%) patients, respectively. In Kaplan-Meier analysis, AAV patients with AIP ≥ 0.11 had significantly lower CVA-free survival rates than in those with AIP < 0.11 (P = 0.027), whereas there was no difference in CAD according to AIP (P = 0.390). Multivariable Cox analysis indicated that AIP ≥ 0.11 at diagnosis was the sole predictor of CVA (Hazard ratio 3.392, 95% confidence interval 1.076, 10.696, P = 0.037).

Conclusions
AIP is significantly higher in AAV patients than in healthy controls, and AIP ≥ 0.11 at diagnosis is a significant predictor of CVA during follow-up. Stringent surveillance should be provided in AAV patients with AIP ≥ 0.11 regarding the occurrence of CVA.

Trial registration
Retrospectively registered (4–2017-0673).
Cytomegalovirus and disseminated histoplasmosis-related hemophagocytic lymphohistiocytosis syndrome in an HIV-patient late presenter with IRIS: a case report
Authors: González-Hernández Luz A. , Alvarez-Zavala Monserrat , Cabrera-Silva Rodolfo I. , Martínez-Ayala Pedro , Amador-Lara Fernando , Ramírez-González Aída S. , Ron-Magaña Ana L. , Ruiz Herrera Vida V. , Sánchez-Reyes Karina , Andrade-Villanueva Jaime F. 
Published: August 2020

AbstractBackgroundHemophagocytic lymphohistiocytosis syndrome (HLS) is an immune-mediated life-threatening disease considered as a medical emergency, with a potentially fatal multisystem inflammatory outcome. We present a patient that developed HLS and was able to be diagnosed efficiently with the help of an academic research institute of immunology.Case presentationA 21 years old male Mexican with human immunodeficiency virus (HIV), late presenter; who developed cytomegalovirus (CMV) infection and a disseminated histoplasmosis-related HLS, as part of an immune reconstitution inflammatory syndrome (IRIS). The patient required a long course of corticotherapy, intravenous immunoglobulin and massive transfusions (more than 10 units in 24 h, and a total of 83 units), besides amphotericin-B and ganciclovir treatment. An academic research institute of immunology aided in the accurate diagnosis of HLS with the implementation of tests not available within the hospital, thus improving the care provided to the patient. The patient recovered, was discharged, and continue to improve.ConclusionThe objective of this report is to highlight the importance of having multidisciplinary support, including basic medical sciences groups providing specific tests that are sometimes very difficult to get, which provides a benefit to patients in the well-aimed diagnosis as part of applied translational medicine.
Low vitamin D levels in post-menopausal women are associated with complex regional pain syndrome type I in surgically treated distal radius fractures
Authors: Lee Sang-Uk , Na Ki-Tae , Lee Yoon-Min , Park Jong Hwa , Joo Sun Young 
Published: August 2020

AbstractBackgroundComplex regional pain syndrome type I (CRPS I) is a chronic devastating condition and a relatively common complication of distal radius fractures (DRF). The purpose of this study was to investigate the relationship of vitamin D levels in surgically treated post-menopausal women with CRPS I occurrence in DRF.MethodsFrom February 2016 to March 2017, 158 surgically treated post-menopausal patients with DRF were enrolled. Exclusion criteria were (1) patients who had been taking vitamin D or osteoporosis medication at the time of injury; (2) patients with medical factors that may affect vitamin D levels; (3) patients who were reluctant to enroll in the study; and (4) patient with additional fractures, ligamentous injuries, or neuropathy. A total of 107 patients were available for final analysis. We compared the serum vitamin D levels in post-menopausal women with DRF with CRPS I (group 1) and without CRPS I (group 2). Bone mineral density (BMD) of the femur and spine, osteocalcin, alkaline phosphatase (ALP), body mass index (BMI) were also measured.ResultsThe average age at the time of surgery was 66.5 years (range, 39-86 years). The mean follow-up period was 16.3 months after surgery. Among the 107 surgically treated DRF patients, 19 (18%) met the Budapest criteria for CRPS I during the follow-up period. The mean serum vitamin D level in group 1 (15.2 ng/ml) was significantly lower than that in group 2 (20.5 ng/ml,p= 0.027). The mean values of osteocalcin, ALP, BMI, and BMD were not significantly different between the groups.ConclusionLower vitamin D levels in post-menopausal women can increase CRPS I occurrence in distal radius fractures.
Targeting activated PI3K/mTOR signaling overcomes acquired resistance to CDK4/6-based therapies in preclinical models of hormone receptor-positive breast cancer
Authors: O’Brien Neil A. , McDermott Martina S. J. , Conklin Dylan , Luo Tong , Ayala Raul , Salgar Suruchi , Chau Kevin , DiTomaso Emmanuelle , Babbar Naveen , Su Faye , Gaither Alex , Hurvitz Sara A. , Linnartz Ronald , Rose Kristine , Hirawat Samit , Slamon Dennis J. 
Published: August 2020

AbstractBackgroundCombined targeting of CDK4/6 and ER is now the standard of care for patients with advanced ER+/HER2− breast cancer. However, acquired resistance to these therapies frequently leads to disease progression. As such, it is critical to identify the mechanisms by which resistance to CDK4/6-based therapies is acquired and also identify therapeutic strategies to overcome resistance.MethodsIn this study, we developed and characterized multiple in vitro and in vivo models of acquired resistance to CDK4/6-based therapies. Resistant models were screened by reverse phase protein array (RPPA) for cell signaling changes that are activated in resistance.ResultsWe show that either a direct loss of Rb or loss of dependence on Rb signaling confers cross-resistance to inhibitors of CDK4/6, while PI3K/mTOR signaling remains activated. Treatment with the p110α-selective PI3K inhibitor, alpelisib (BYL719), completely blocked the progression of acquired CDK4/6 inhibitor-resistant xenografts in the absence of continued CDK4/6 inhibitor treatment in models of bothPIK3CAmutant and wild-type ER+/HER2− breast cancer. Triple combination therapy against PI3K:CDK4/6:ER prevented and/or delayed the onset of resistance in treatment-naive ER+/HER2− breast cancer models.ConclusionsThese data support the clinical investigation of p110α-selective inhibitors of PI3K, such as alpelisib, in patients with ER+/HER2− breast cancer who have progressed on CDK4/6:ER-based therapies. Our data also support the investigation of PI3K:CDK4/6:ER triple combination therapy to prevent the onset of resistance to the combination of endocrine therapy plus CDK4/6 inhibition.
Methods for copy number aberration detection from single-cell DNA-sequencing data
Authors: Mallory Xian F. , Edrisi Mohammadamin , Navin Nicholas , Nakhleh Luay 
Published: August 2020

AbstractCopy number aberrations (CNAs), which are pathogenic copy number variations (CNVs), play an important role in the initiation and progression of cancer. Single-cell DNA-sequencing (scDNAseq) technologies produce data that is ideal for inferring CNAs. In this review, we review eight methods that have been developed for detecting CNAs in scDNAseq data, and categorize them according to the steps of a seven-step pipeline that they employ. Furthermore, we review models and methods for evolutionary analyses of CNAs from scDNAseq data and highlight advances and future research directions for computational methods for CNA detection from scDNAseq data.
Robotic-arm assisted medial unicondylar knee arthroplasty versus jig-based unicompartmental knee arthroplasty with navigation control: study protocol for a prospective randomised controlled trial
Authors: Kayani Babar , Konan Sujith , Tahmassebi Jenni , Ayuob Atif , Moriarty Peter D. , Haddad Fares S. 
Published: August 2020

Abstract
Background
There remains a paucity of clinical studies assessing how any differences in accuracy of implant positioning between robotic-arm assisted unicompartmental knee arthroplasty (RO UKA) and conventional jig-based unicompartmental knee arthroplasty (CO UKA) translate to patient satisfaction, functional outcomes, and implant survivorship. The objectives of this study are to compare accuracy of implant positioning, limb alignment, patient satisfaction, functional outcomes, implant survivorship, cost-effectiveness, and complications in CO UKA versus RO UKA. Computer navigation will be used to assess intraoperative knee kinematics in all patients undergoing CO UKA.

Methods and analysis
This prospective randomised controlled trial will include 140 patients with symptomatic medial compartment knee arthritis undergoing primary UKA. Following informed consent, patients will be randomised to CO UKA (control group) or RO UKA (investigation group) at a ratio of 1:1 using an online random number generator. The primary objective of this study is to compare accuracy of implant positioning in CO UKA versus RO UKA. The secondary objectives are to compare the following outcomes between the two treatment groups: limb alignment, surgical efficiency, postoperative functional rehabilitation, functional outcomes, quality of life, range of motion, resource use, cost effectivness, and complications. Observers will review patients at regular intervals for 2 years after surgery to record predefined study outcomes pertaining to these objectives. Ethical approval was obtained from the London-Bloomsbury Research Ethics Committee, UK. The study is sponsored by University College London, UK.

Discussion
This study compares a comprehensive and robust range of clinical, functional, and radiological outcomes in CO UKA versus RO UKA. The findings of this study will provide an improved understanding of the differences in CO UKA versus RO UKA with respect to accuracy of implant positioning, patient satisfaction, functional outcomes, implant survivorship, cost-effectiveness, and complications.

Trial registration
ClinicalTrials.gov NCT04095637. Registered on 19 September 2019.