bluuebunny/crossref_metadata_2025_split huggingface dataset:
Widely used, short 16S rRNA mitochondrial gene fragments yield poor and erratic results in phylogenetic estimation and species delimitation of amphibians
Authors: Chan Kin Onn , Hertwig Stefan T. , Neokleous Dario N. , Flury Jana M. , Brown Rafe M. 
Published: March 2022

AbstractBackgroundThe 16S mitochondrial rRNA gene is the most widely sequenced molecular marker in amphibian systematic studies, making it comparable to the universalCO1barcode that is more commonly used in other animal groups. However, studies employ different primer combinations that target different lengths/regions of the 16S gene ranging from complete gene sequences (~ 1500 bp) to short fragments (~ 500 bp), the latter of which is the most ubiquitously used. Sequences of different lengths are often concatenated, compared, and/or jointly analyzed to infer phylogenetic relationships, estimate genetic divergence (p-distances), and justify the recognition of new species (species delimitation), making the 16S gene region, by far, the most influential molecular marker in amphibian systematics. Despite their ubiquitous and multifarious use, no studies have ever been conducted to evaluate the congruence and performance among the different fragment lengths.ResultsUsing empirical data derived from both Sanger-based and genomic approaches, we show that full-length 16S sequences recover the most accurate phylogenetic relationships, highest branch support, lowest variation in genetic distances (pairwisep-distances), and best-scoring species delimitation partitions. In contrast, widely used short fragments produce inaccurate phylogenetic reconstructions, lower and more variable branch support, erratic genetic distances, and low-scoring species delimitation partitions, the numbers of which are vastly overestimated. The relatively poor performance of short 16S fragments is likely due to insufficient phylogenetic information content.ConclusionsTaken together, our results demonstrate that short 16S fragments are unable to match the efficacy achieved by full-length sequences in terms of topological accuracy, heuristic branch support, genetic divergences, and species delimitation partitions, and thus, phylogenetic and taxonomic inferences that are predicated on short 16S fragments should be interpreted with caution. However, short 16S fragments can still be useful for species identification, rapid assessments, or definitively coupling complex life stages in natural history studies and faunal inventories. While the full 16S sequence performs best, it requires the use of several primer pairs that increases cost, time, and effort. As a compromise, our results demonstrate that practitioners should utilize medium-length primers in favor of the short-fragment primers because they have the potential to markedly improve phylogenetic inference and species delimitation without additional cost.
High-flow nasal cannula in nonlaser microlaryngoscopic surgery: a prospective study of 19 cases in a chinese population
Authors: Ma Bo , Liu Fei , Wang Dandan , Zhong Ruihan , Lin Kaihao , Li Shuo , Zhang Jie , Li Chaoyang 
Published: March 2022

Abstract
Background
High-flow nasal cannula (HFNC) is a new type of oxygen therapy, but its application in surgery remains unclear, we tried to describe the application of HFNC in microlaryngoscopic surgery for the Chinese population.

Methods
Nineteen adults, American society of anesthesiology class (ASA) 1–2 patients with body mass index < 30 kg.m−2 underwent microlaryngoscopic surgery using HFNC for airway management. Outcomes included apnoea time, intraoperative oxygenation, carbon dioxide value, lactate value, and the relationship between the duration of apnoea time and carbon dioxide levels.

Results
A total of 19 patients underwent vocal cord tumor resection under a microlaryngoscope with HFNC as the sole method of ventilation. The mean age was 39.7 years old, and the mean BMI was 23.9 kg.m−2. The mean apnea time was 21.5 min. The SpO2 of 18 patients remained above 90%, and only 1 patient dropped to 88%. The average basal lactate and highest lactate value was 0.58 mmol. L−1 and 0.68 mmol.L−1. The difference between basal and highest lactate values was statistically significant (P < 0.05). The average highest PaCO2 value was 79.4 mmHg. The PaCO2 increased by 1.68 ± 0.12 mmHg every minute linearly.

Conclusions
In the case series we have observed that HFNC would be safe and effective oxygenation and ventilation technique for selected Chinese patients undergoing non-laser microlaryngoscopic surgery within 30 min. The tubeless technology reduces the complications of tracheal intubation and jet ventilation and clears the surgical field of vision.

Trial registration
Chinese Clinical Trial Registry (ChiCTR100049144).
MedMinas project: design and use of mixed methods in the evaluation of pharmaceutical services in primary health care in Minas Gerais, Brazil
Authors: Luz Tatiana Chama Borges , Tavares Noemia Urruth Leão , de Castro Ana Karine Sarvel , Marques Isabela Cristina , dos Santos Elizabeth Moreira , Cota Betania Barros 
Published: March 2022

AbstractBackgroundThe main purposes of primary care-based pharmaceutical services (PHCPS) in Brazil are to provide free access to medicines and pharmaceutical care to patients. Several obstacles hinder achieving their goals; thus, MedMinas Project aimed to evaluate the PHCPS, the supply system, and the use of medicines. This paper reflects on our experience designing, planning, and conducting the project, describing the issues yielded in the field and lessons learned.MethodsThis work consists of a mixed-methods study conducted in Minas Gerais, Southeastern Brazil. We adopted the principles of Rapid Evaluation Methods, employing a multistage stratified sampling for the quantitative and a purposeful sampling for the qualitative components, respectively, and a documentary research. Data sources included individuals (patients and professionals), prescriptions, dispensed medicines, and policy documents collected between April and October 2019. The quantitative data described in this paper were analysed by descriptive statistics and the qualitative by Thematic Content Analysis.ResultsA total of 26 municipalities varying from 37,784 to 409,341 inhabitants were included. The field team spent, on average, 16 days in each location. We interviewed 1019 respondents, of which 127 were professionals and 892 patients. The participation rate varied from 92 to 100%, depending on the respondent subgroup. Most interviews lasted between 45 min and one hour. Fieldwork challenges included participants’ enrolment, field team, interview processes, and project budget. The participants provided positive feedback and five main themes emerged from the interview experience (self-awareness, sense of gratitude, research value, access to findings, and benefits of the research). Additionally, we collected copies of 1072 documents and 2070 pieces of data from prescriptions filled and medicines dispensed at the PCP.ConclusionWe demonstrated the viability of conducting the MedMinas Project in an extensive geographic area within effective time frames that provided meaningful, high-quality data from multiple actors. The methods and lessons learned are valuable for researchers across various disciplines in similar urban settings in Brazil and other countries of low- and middle-income (LMIC).
Anti-NMDAR encephalitis with bilateral basal ganglia MRI lesions at a distance of time: a case report
Authors: Son Dong Keun , Cho Seong Min , Ryu Han Uk , Shin Byoung-Soo , Kang Hyun Goo 
Published: March 2022

Abstract
Background
Approximately half (55%) of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is known to show abnormal brain images, including high signal intensity in T2 or fluid attenuated inversion recovery (FLAIR) images. In a minority of anti-NMDAR encephalitis cases, high signal intensity on diffusion-weighted imaging (DWI) has been reported, a finding that is highly suggestive of a stroke.

Case presentation
We present the case of a 66-year-old man who experienced two separate focal seizure events, which involved first the right and then the left upper extremity in a short period of time. The patient showed focal clonic seizures involving right arm and hand, which sometimes evolved to bilateral tonic-clonic seizures on his first admission. Brain magnetic resonance imaging (MRI) showed high signal intensity on DWI and low signal intensity on the apparent diffusion coefficient (ADC) map of the left caudate nucleus and putamen. The patient was discharged symptom-free with anti-epileptic drugs for 2 weeks. The second admission occurred 4 days after the discharge. He exhibited a new symptom of focal clonic seizures involving left arm and hand while showing a brain lesion on the opposite side which is hyperintense on DWI image and hypointense on ADC map. The patient was eventually diagnosed with anti-NMDAR encephalitis according to the cerebrospinal fluid (CSF) antibody test.

Conclusions
This is the case of anti-NMDAR encephalitis patient whose DWI/ADC images revealed sequential involvement on the left and right basal ganglia with a short time interval. When stroke-like brain lesions on DWI are found in a patient with a focal seizure, a CSF study could help rule out autoimmune encephalitis. We also suggest that DWI/ADC map images may be useful for the early detection of anti-NMDAR encephalitis.
N-glycolylneuraminic acid serum biomarker levels are elevated in breast cancer patients at all stages of disease
Authors: Shewell Lucy K. , Day Christopher J. , Kutasovic Jamie R. , Abrahams Jodie L. , Wang Jing , Poole Jessica , Niland Colleen , Ferguson Kaltin , Saunus Jodi M. , Lakhani Sunil R. , von Itzstein Mark , Paton James C. , Paton Adrienne W. , Jennings Michael P. 
Published: March 2022

Abstract
Background
Normal human tissues do not express glycans terminating with the sialic acid N-glycolylneuraminic acid (Neu5Gc), yet Neu5Gc-containing glycans have been consistently found in human tumor tissues, cells and secretions and have been proposed as a cancer biomarker. We engineered a Neu5Gc-specific lectin called SubB2M, and previously reported elevated Neu5Gc biomarkers in serum from ovarian cancer patients using a Surface Plasmon Resonance (SPR)-based assay. Here we report an optimized SubB2M SPR-based assay and use this new assay to analyse sera from breast cancer patients for Neu5Gc levels.

Methods
To enhance specificity of our SPR-based assay, we included a non-sialic acid binding version of SubB, SubBA12, to control for any non-specific binding to SubB2M, which improved discrimination of cancer-free controls from early-stage ovarian cancer. We analysed 96 serum samples from breast cancer patients at all stages of disease compared to 22 cancer-free controls using our optimized SubB2M-A12-SPR assay. We also analysed a collection of serum samples collected at 6 monthly intervals from breast cancer patients at high risk for disease recurrence or spread.

Results
Analysis of sera from breast cancer cases revealed significantly elevated levels of Neu5Gc biomarkers at all stages of breast cancer. We show that Neu5Gc serum biomarker levels can discriminate breast cancer patients from cancer-free individuals with 98.96% sensitivity and 100% specificity. Analysis of serum collected prospectively, post-diagnosis, from breast cancer patients at high risk for disease recurrence showed a trend for a decrease in Neu5Gc levels immediately following treatment for those in remission.

Conclusions
Neu5Gc serum biomarkers are a promising new tool for early detection and disease monitoring for breast cancer that may complement current imaging- and biopsy-based approaches.
Safety and efficacy study of laparoscopic or robotic radical surgery using an endoscopic stapler for inhibiting tumour spillage of cervical malignant neoplasms evaluating survival (SOLUTION): a multi-centre, open-label, single-arm, phase II trial protocol
Authors: Park Soo Jin , Kong Tae Wook , Kim Taehun , Lee Maria , Choi Chel Hun , Shim Seung-Hyuk , Yim Ga Won , Lee Seungmee , Lee Eun Ji , Lim Myong Cheol , Chang Suk-Joon , Lee Sung Jong , Lee San Hui , Song Taejong , Lee Yoo-Young , Kim Hee Seung , Nam Eun Ji 
Published: March 2022

Abstract
Background
The Laparoscopic Approach to Cervical Cancer trial and Surveillance, Epidemiology, and End Results program database study demonstrated that minimally invasive radical hysterectomy was inferior to abdominal radical hysterectomy in terms of disease recurrence and survival. Among risk factors related to poor prognosis after minimally invasive surgery (MIS), tumour spillage during intracorporeal colpotomy became a significant issue. Thus, we designed this trial to evaluate the efficacy and safety of minimally invasive radical hysterectomy using an endoscopic stapler for early-stage cervical cancer.

Methods
This trial is a prospective, multi-centre, open-label, single-arm, non-inferiority phase II study. The nine organisations will participate in this trial after the approval of the institutional review board. Major eligibility criteria include women aged 20 years or older with cervical cancer stage IB1 squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma according to the revised 2009 FIGO staging system who will undergo type B2 or C hysterectomy by MIS. The primary endpoint is the 4.5-year disease-free survival (DFS) rate between abdominal radical hysterectomy and MIS using an endoscopic stapler. For calculating the sample size, we hypothesised that the 4.5-year DFS rate after MIS using an endoscopic stapler is assumed to be the same after abdominal radical hysterectomy at 90.9%, and the non-inferiority margin was 7.2%. When we consider a three-year accrual and 4.5-year follow-up, at least 13 events must happen, requiring a total of 111 patients assuming a statistical power of 80% and the one-tailed test of 5% significance. A total of 124 patients is needed, considering a drop-out rate of 10%.

Discussion
We expect intracorporeal colpotomy using an endoscopic stapler may prevent tumour spillage during MIS for stage IB1 cervical cancer, showing a comparable prognosis with abdominal radical surgery.

Trial registration
ClinicalTrials.gov; NCT04370496; registration date, May 2020.
The trend of 10-year cardiovascular risk among diabetic and non-diabetic participants in Tehran Lipid and glucose study: 1999–2018
Authors: Koohi Fatemeh , Kohansal Karim , Naz Marzieh Saei Ghare , Derakhshan Somayeh , Azizi Fereidoun , Khalili Davood 
Published: March 2022

Abstract
Background
Assessing the risk of cardiovascular disease (CVD) is crucial in preventive cardiology. We aimed to determine the trend of CVD risk among individuals with and without diabetes during two decades of follow-up in a Middle Eastern cohort.

Methods
We studied 8,450 individuals (55.5% women) aged 40–75 years who participated in the Tehran Lipid and Glucose Study (TLGS). Diabetes status and CVD risk factors were evaluated in six examinations from 1999 to 2018. The individual 10-year CVD risk score was calculated using the ACC/AHA recommended risk equation. We used generalized estimating equation models (GEE) to assess the time trends of CVD risk factors and CVD risk scores in diabetic and non-diabetic groups separately.

Results
The age-adjusted ACC/AHA risk score significantly decreased in non-diabetic women and men (from 3.2% to 1.6% in women and 6.8% to 5.0% in men; p for trend < 0.001). Whereas the risk significantly decreased among diabetics men (from 13.8% to 11.5%), it increased somehow among diabetics women (from 5.3% to 5.5%). Furthermore, in both sexes, diabetic individuals compared to non-diabetic ones had better control on their systolic blood pressure, total cholesterol, and fasting plasma glucose during the last two decades.

Conclusions
The CVD risk and most CVD risk factors improved in individuals with and without diabetes in the past two decades; however, they have not reached the targets yet. So, more stringent lifestyle modifications and treatment strategies are needed, especially for primary prevention in the general population.
Interaction between posaconazole and flucloxacillin in a lung transplant patient: decrease in plasma exposure of posaconazole and possible undertreatment of invasive aspergillosis: case report
Authors: Verfaillie Saartje , Godinas Laurent , Spriet Isabel , Vos Robin , Verleden Geert M. 
Published: March 2022

Abstract
Background
Variability in triazole plasma concentrations by drug interactions is well known. An interaction between voriconazole and flucloxacillin has already been described. In our case we observed a similar interaction between posaconazole and flucloxacillin, which in our knowledge has not ever been reported in literature.

Case presentation
A 60-year-old male who had a double lung transplantation for end-stage chronic obstructive pulmonary disease was being treated with voriconazole for invasive pulmonary aspergillosis (IPA). During this treatment he presented at the emergency room and was diagnosed with endocarditis for which a combination of amoxicillin, flucloxacillin and gentamicin was initiated. A known interaction between voriconazole and flucloxacillin was observed, with a drop of the voriconazole levels, and treatment for IPA was switched to posaconazole. After ending the treatment for endocarditis, the patient had a catheter infection for which flucloxacillin was reinitiated. Unexpectedly we saw a similar immediate drop in posaconazole levels, recovering after ending treatment with flucloxacillin.

Conclusions
We describe a new interaction between posaconazole and flucloxacillin. Presumably the underlying mechanism is activation of the pregnane X receptor by flucloxacillin, which can induce cytochrome P450, uridine glucuronosyl transferase (UGT1A4) and P-glycoprotein. We advise caution when combining flucloxacillin and triazoles, because interactions may lead to undertreatment of invasive aspergillosis.
The zinc transporter ZIP12 regulates monocrotaline-induced proliferation and migration of pulmonary arterial smooth muscle cells via the AKT/ERK signaling pathways
Authors: Ye Chaoyi , Lian Guili , Wang Tingjun , Chen Ai , Chen Weixiao , Gong Jin , Luo Li , Wang Huajun , Xie Liangdi 
Published: March 2022

Abstract
Background
The zinc transporter ZIP12 is a membrane-spanning protein that transports zinc ions into the cytoplasm from the extracellular space. Recent studies demonstrated that upregulation of ZIP12 is involved in elevation of cytosolic free zinc and excessive proliferation of pulmonary arterial smooth muscle cells (PASMCs) induced by hypoxia. However, the expression of ZIP12 and its role in pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT) in rats have not been evaluated previously. The aim of this study was to investigate the effect of ZIP12 on the proliferation and migration of PASMCs and its underlying mechanisms in MCT-induced PAH.

Methods
A PAH rat model was generated by intraperitoneal injection of 20 mg/kg MCT twice at one-week intervals. PASMCs were isolated from the pulmonary arteries of rats with MCT-induced PAH or control rats. The expression of ZIP12 and related molecules was detected in the lung tissues and cells. A ZIP12 knockdown lentivirus and an overexpressing lentivirus were constructed and transfected into PASMCs derived from PAH and control rats, respectively. EdU assays, wound healing assays and Western blotting were carried out to explore the function of ZIP12 in PASMCs.

Results
Increased ZIP12 expression was observed in PASMCs derived from MCT-induced PAH rats. The proliferation and migration of PASMCs from PAH rats were significantly increased compared with those from control rats. These results were corroborated by Western blot analysis of PCNA and cyclin D1. All these effects were significantly reversed by silencing ZIP12. Comparatively, ZIP12 overexpression resulted in the opposite effects as shown in PASMCs from control rats. Furthermore, selective inhibition of AKT phosphorylation by LY294002 abolished the effect of ZIP12 overexpression on enhancing cell proliferation and migration and partially suppressed the increase in ERK1/2 phosphorylation induced by ZIP12 overexpression. However, inhibition of ERK activity by U0126 resulted in partial reversal of this effect and did not influence an increase in AKT phosphorylation induced by ZIP12 overexpression.

Conclusions
ZIP12 is involved in MCT-induced pulmonary vascular remodeling and enhances the proliferation and migration of PASMCs. The mechanism of these effects was partially mediated by enhancing the AKT/ERK signaling pathways.
Unusual manifestations of young woman with MODY5 based on 17q12 recurrent deletion syndrome
Authors: Cheng Ying , Zhong Da-Peng , Ren Li , Yang Hang , Tian Chen-Fu 
Published: March 2022

Abstract
Background
Maturity-onset diabetes of the young type 5 (MODY5) is a rare subtype of MODYs. It is caused by mutations of the hepatocyte nuclear factor 1 homeobox b gene (HNF1B). 17q12 recurrent deletion syndrome usually results in MODY5 because of the deletion of HNF1B. These patients often have other clinical manifestations besides diabetes. Refractory hypomagnesemia was a clue for further examination in this patient. But she lacked structural abnormalities of the genitourinary system and neurodevelopmental disorders that are common manifestations in patients with 17q12 recurrent deletion syndrome. Some atypical patients deserved attention.

Case presentation
A 21-year-old young woman was admitted to our hospital for severe malnutrition and gastrointestinal symptoms. At age 20, she was diagnosed with type 2 diabetes mellitus (T2DM) and was administered oral antidiabetic drugs. Soon afterward, the patient discontinued the medication on her own accord and then went to the hospital again due to diabetic ketoacidosis. After insulin treatment, diabetic ketoacidosis was cured and blood glucose was controlled satisfactorily. But intractable nausea, vomiting, and persistent weight loss were stubborn. Further examination revealed that the patient had hypokalemia and hard rectification hypomagnesemia. Genetic testing revealed about 1.85 Mb heterozygous fragment deletion on chromosome 17 and deletion of exons 1–9 of HNF1B heterozygosity missing was approved. Finally, the patient was diagnosed MODY5.

Discussion and Conclusions
The 17q12 recurrent deletion syndrome is characterized by MODY5, structural or functional abnormalities of the kidney and urinary tract, and neurodevelopmental or neuropsychiatric disorders. This patient did not have any structural abnormalities of the genitourinary system and neuropsychiatric disorders, which is rare. She had experienced a period of misdiagnosis before being diagnosed with 17q12 recurrent deletion syndrome, and hypomagnesemia was an important clue for her diagnosis. Therefore, diabetic physicians should be alert to a special type of diabetes if patients have unexplained signs and symptoms. The absence of well-known features of HNF1B disease does not exclude MODY5.