bluuebunny/crossref_metadata_2025_split huggingface dataset:
A mobile restriction–modification system provides phage defence and resolves an epigenetic conflict with an antagonistic endonuclease
Authors: Birkholz Nils , Jackson Simon A , Fagerlund Robert D , Fineran Peter C 
Published: February 2022

AbstractEpigenetic DNA methylation plays an important role in bacteria by influencing gene expression and allowing discrimination between self-DNA and intruders such as phages and plasmids. Restriction–modification (RM) systems use a methyltransferase (MTase) to modify a specific sequence motif, thus protecting host DNA from cleavage by a cognate restriction endonuclease (REase) while leaving invading DNA vulnerable. Other REases occur solitarily and cleave methylated DNA. REases and RM systems are frequently mobile, influencing horizontal gene transfer by altering the compatibility of the host for foreign DNA uptake. However, whether mobile defence systems affect pre-existing host defences remains obscure. Here, we reveal an epigenetic conflict between an RM system (PcaRCI) and a methylation-dependent REase (PcaRCII) in the plant pathogen Pectobacterium carotovorum RC5297. The PcaRCI RM system provides potent protection against unmethylated plasmids and phages, but its methylation motif is targeted by the methylation-dependent PcaRCII. This potentially lethal co-existence is enabled through epigenetic silencing of the PcaRCII-encoding gene via promoter methylation by the PcaRCI MTase. Comparative genome analyses suggest that the PcaRCII-encoding gene was already present and was silenced upon establishment of the PcaRCI system. These findings provide a striking example for selfishness of RM systems and intracellular competition between different defences.
Cardiac magnetic resonance in systemic sclerosis myocarditis: the value of T2 mapping to detect myocardial inflammation
Authors: De Luca Giacomo , Palmisano Anna , Campochiaro Corrado , Vignale Davide , Cavalli Giulio , Bruno Elisa , Sartorelli Silvia , Ferlito Arianna , Peretto Giovanni , Sala Simone , Matucci-Cerinic Marco , Dagna Lorenzo , Esposito Antonio 
Published: February 2022

AbstractObjectivesMyocarditis in SSc is associated with a poor prognosis. Cardiac magnetic resonance (CMR) is the non-invasive diagnostic modality of choice for SSc myocarditis. Our study investigates the performance of the mapping techniques included in the revised Lake Louise criteria (LLC) for the identification of SSc myocarditis.MethodsCMR data (right and left ventricular function and morphology, early and late gadolinium enhancement [LGE], T2 ratio, and T1 mapping, extracellular volume [ECV] and T2 mapping) of SSc patients diagnosed with myocarditis were reviewed. Myocarditis was defined by the presence of symptoms of SSc heart involvement with increased high-sensitive troponin T (hs-TnT) and/or NT-proBNP and at least an abnormality at 24 h ECG Holter and/or echocardiography and/or CMR. A P-value &lt; 0.05 was considered as statistically significant.ResultsNineteen patients (median age 54 [46–70] years; females 78.9%; diffuse SSc 52.6%; anti-Scl70+ 52.6%) were identified: 11 (57.9%) had echocardiographic, and 8 (42.8%) 24 h ECG Holter abnormalities. All patients had at least one CMR abnormality: LGE in 18 (94.7%), increased ECV in 10 (52.6%) and T2 mapping &gt;50 ms in 15 (78.9%). Median T1 and T2 mapping were 1085 [1069–1110] ms and 53.1 [52–54] ms, respectively. T1 mapping directly correlated with NT-proBNP (r = 0.620; P = 0.005), ESR (r = 0.601; P = 0.008), CRP (r = 0.685; P = 0.001) and skin score (r = 0.507; P = 0.027); ECV correlated with NT-proBNP serum levels (r = 0.702; P = 0.001). No correlations emerged between T2 mapping and other parameters. Ten patients satisfied the 2009 LLC, 17 the 2018 LLC. With the new criteria including T2 mapping, the sensitivity improved from 52.6% to 89.5%.ConclusionThe CMR mapping techniques improve the sensitivity to detect myocardial inflammation in patients with SSc heart involvement. The evaluation of T2 mapping increases diagnostic accuracy for the recognition of myocardial inflammation in SSc.
Semaglutide for weight loss and cardiometabolic risk reduction in overweight/obesity
Authors: Mares Adriana C. , Chatterjee Saurav , Mukherjee Debabrata 
Published: February 2022

Purpose of review
Cardiovascular disease is the most common cause of morbidity and mortality worldwide, and the risk is heightened in the presence of obesity. We review semaglutide, a drug recently approved for chronic weight management in adults with obesity or who are overweight.

Recent findings
On 4 June 2021, the US Food and Drug Administration approved semaglutide injection at 2.4 mg once weekly for chronic weight management in adults with obesity or overweight with at least one weight-related condition such as high blood pressure, type 2 diabetes mellitus, or high cholesterol. This subcutaneous injection is the first approved drug for chronic weight management in adults with general obesity or overweight since 2014. The drug is indicated for weight management in patients with a BMI of 27 kg/m2 or greater who have at least one weight-related ailment or in patients with a BMI of 30 kg/m2 or greater.

Summary
Semaglutide offers adults with obesity or overweight a new treatment in conjunction with a weight management program consisting of reduced calorie diet and increased physical activity.
OUTCOMES OF RETROPUPILLARY IRIS CLAW INTRAOCULAR LENS IMPLANTATION COMBINED WITH PARS PLANA VITRECTOMY
Authors: Zaleski Marta , Stahel Marc , Eberhard Roman , Alexander Blum Robert , Barthelmes Daniel 
Published: February 2022

Purpose:
To report 12-month visual outcomes, incidence of intraocular pressure (IOP) changes and postoperative complications after pars plana vitrectomy with retropupillary implantation of an iris claw intraocular lens (IOL) in aphakic eyes after complicated cataract surgery and eyes with a dislocation of the IOL.

Methods:
This is a retrospective analysis of eyes undergoing implantation of an iris claw IOL combined with pars plana vitrectomy from 1st of January 2009 until 30th of June 2018 after complicated cataract extraction with capsular loss (Group A) or dislocation of an IOL (Group B). Corrected distance visual acuity was analyzed in logarithm of the minimum angle of resolution (logMAR) units, IOP was recorded in mmHg.

Results:
Eyes in Group A (n = 49) improved from a preoperative median visual acuity of 0.523 logMAR (Snellen 20/65) to 0.201 logMAR (Snellen 20/30), P < 0.01. Eyes in Group B (n = 126) showed stable median visual acuity, preoperative 0.301 logMAR (Snellen 20/40) versus postoperative 0.222 logMAR (Snellen 20/30), P > 0.05. During 12 months in Group A, IOP >21 mmHg occurred in 9 (18.4%) eyes; no eye had an IOP <6 mmHg. In Group B, IOP >21 mmHg occurred in 15 (11.9%) eyes, IOP <6 mmHg in 5 (4%) cases. None of the eyes in Group A and B had IOP >21 mmHg or <6 mmHg at 12 months follow-up.

Conclusion:
The retropupillary implantation of an iris claw IOL with pars plana vitrectomy provides adequate visual rehabilitation and seems to be safe in IOP changes.
Risk Factors and Treatment of Clostridioides difficile in Pediatric Patients
Authors: Nang Catherine 
Published: February 2022

Abstract
The purpose of this article is to discuss the pharmacological causes of pediatric Clostridioides difficile infection (CDI) and the treatment options available to clinicians. The authors identify antibiotic classes and antacids and how they interfere with normal gastrointestinal processes to cause CDI. In addition, the treatment algorithm for pediatric patients, which differs slightly from adults, is presented. Choosing the appropriate medication is imperative in reducing symptoms, recurrence, and optimizing treatment of CDI. This article will discuss the medications that contribute to CDI and not cover infectious causes or structural causes.
Biomechanical and Musculoskeletal Differences Between Postpartum Runners and Nulliparous Controls
Authors: Christopher Shefali Mathur , Bauer Lindsey , Maylone Rebba , Bullock Garrett S. , Chinworth Susan A. , Snodgrass Suzanne J. , Vallabhajosula Srikant 
Published: February 2022

Background:
Women are running as soon as 8 weeks postpartum and there is currently little understanding of the effects of pregnancy and childbirth on the postpartum runner (PPR). Pregnancy-related musculoskeletal and physiological changes could impact running gait postpartum.

Objective:
The purpose of the current study was to investigate differences in overground running kinetics, strength and flexibility in PPRs, and age-matched nulliparous controls.

Methods:
Vertical and anteroposterior ground reaction force (APGRF) data were collected during overground running and normalized to body weight (NBW). Hip and knee strength, and hamstring flexibility measures were collected using a handheld dynamometer and inclinometer, respectively. Data were averaged for both legs. Independent-samples t tests and effect size (ES) estimations were conducted using α = .05.

Findings:
Nine PPRs (33.10 ± 5.60 years; ≤2 years postpartum) and 9 age-matched nulliparous women (31.67 ± 4.55 years) participated. PPRs had 24.3% greater braking loading rate for APGRF than controls (mean difference [MD] 3.41 NBW/s, 95% confidence interval [CI] 0.08, 6.74; P = .046; ES 1.08). PPRs had 14% less hamstring flexibility (MD 10.98°, 95% CI 0.97, 20.99; P = .034; ES 1.14), 25.9% less hip abduction strength (MD 0.04 NBW, 95% CI 0.00, 0.08; P = .045; ES 1.07) and 51.6% less hip adduction strength (MD 0.06 NBW, 95% CI 0.02, 0.10; P = .003; ES 1.68).

Interpretation:
These preliminary findings suggest that PPRs demonstrate altered running braking strategies and decreased hamstring flexibility and hip strength compared with nulliparous controls. As running guidelines for PPRs have been derived mostly from expert opinion, this exploratory cohort study suggests that PPRs should be evaluated for musculoskeletal impairments before initiating or returning to running. (See the Video, Supplemental Digital Content A, available at: http://links.lww.com/JWHPT/A67, which discusses the significance, innovation, and clinical applicability of this study.)
Systemic Vasculitis Following SARS-CoV-2 mRNA Vaccination Demonstrated on FDG PET/CT
Authors: Nakatani Koya , Sakata Etsuro , Fujihara Masakazu , Mizukawa Kaoru , Koyama Takashi 
Published: February 2022

Abstract
Causality regarding adverse events following SARS-CoV-2 mRNA vaccine is undetermined for vasculitis. Herein, we report the case of an 80-year-old man who presented with a persistent high fever of 7 days' duration that began shortly after receiving a COVID-19 vaccination. There was also a complaint of persistent lower limb pain and walking difficulty on emergency transportation. FDG PET/CT demonstrated extensive linear hypermetabolic foci along the vessels of both legs, including the hips, and the arms, supraclavicular area, chest wall, and temporal regions, suggesting systemic vasculitis. Subsequent temporal artery biopsy revealed arteritis, which is not typical of giant cell arteritis.
Germline intergenic duplications at Xq26.1 underlie Bazex-Dupré-Christol syndrome, an inherited basal cell carcinoma susceptibility condition
Authors: Liu Yanshan , Banka Siddharth , Huang Yingzhi , Hardman-Smart Jonathan , Pye Derek , Torrelo Antonio , Beaman Glenda M. , Kazanietz Marcelo G. , Baker Martin J , Ferrazzano Carlo , Shi Chenfu , Orozco Gisela , Eyre Stephen , van Geel Michel , Bygum Anette , Fischer Judith , Miedzybrodzka Zosia , Abuzahra Faris , Rübben Albert , Cuvertino Sara , Ellingford Jamie M. , Smith Miriam J. , Evans D. Gareth , Weppner-Parren Lizelotte J.M.T , van Steensel Maurice A.M. , Chaudhary Iskander H. , Mangham D. Chas , Lear John T. , Paus Ralf , Frank Jorge , Newman William G. , Zhang Xue 
Published: February 2022

AbstractBackgroundBazex-Dupré-Christol syndrome (BDCS; MIM301845) is a rare X-linked dominant genodermatosis characterized by follicular atrophoderma, congenital hypotrichosis and multiple basal cell carcinomas (BCCs). Previous studies have linked BDCS to an 11.4 Mb interval on chromosome Xq25-27.1. However, the genetic mechanism of BDCS remains an open question.MethodsTo investigate the genetic etiology of BDCS, we ascertained eight families with individuals affected with BDCS (F1-F8). Whole exome (F1 and F2) and genome sequencing (F3) were performed to identify putative disease-causing variants within the linkage region. Array-comparative genomic hybridization and quantitative PCR were used to explore copy number variations (CNV) in BDCS families, followed by long-range gap-PCR and Sanger sequencing to amplify duplication junction and define the precise head-tail junctions, respectively. Immunofluorescence was performed in hair follicles, BCCs and trichoepitheliomas from BDCS patients and sporadic BCCs to detect the expression of corresponding genes. The ACTRT1 variant (p.Met183Asnfs*17), previously proposed to cause BDCS, was evaluated with allele frequency calculator.ResultsIn eight BDCS families, we identified overlapping 18-135kb duplications (six inherited and two de novo) at Xq26.1, flanked by ARHGAP36 and IGSF1. We detected ARHGAP36 expression near the control hair follicular stem cells compartment, and found increased ARHGAP36 levels in hair follicles in telogen, BCCs and trichoepitheliomas from patients with BDCS. ARHGAP36 was also detected in sporadic BCCs from individuals without BDCS. Our modelling showed the predicted ACTRT1 variants maximum tolerated minor allele frequency in control populations to be orders of magnitude higher than expected for a high-penetrant ultra-rare disorder, suggesting loss-of-function of ACTRT1 is unlikely to cause BDCS.ConclusionsOur data support the pathogenicity of intergenic duplications at Xq26.1, most likely leading to dysregulation of ARHGAP36, establish BDCS as a genomic disorder, and provide a potential therapeutic target for both inherited and sporadic BCCs.
An optimized reference tissue method for quantification of tau protein depositions in diverse neurodegenerative disorders by PET with 18F-PM-PBB3 (18F-APN-1607)
Authors: Tagai Kenji , Ikoma Yoko , Endo Hironobu , Debnath Oiendrila Bhowmik , Seki Chie , Matsuoka Kiwamu , Matsumoto Hideki , Oya Masaki , Hirata Kosei , Shinotoh Hitoshi , Takahata Keisuke , Kurose Shin , Sano Yasunori , Ono Maiko , Shimada Hitoshi , Kawamura Kazunori , Zhang Ming-Rong , Takado Yuhei , Higuchi Makoto 
Published: February 2022

ABSTRACTPositron emission tomography (PET) with 18F-PM-PBB3 (18F-APN-1607) enables high-contrast detection of tau depositions in various neurodegenerative dementias, including Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD). A simplified method for quantifying the radioligand binding in target regions is to employ the cerebellum as a reference (CB-ref) on the assumption that the cerebellum has minimal tau pathologies. This procedure could be valid in AD, while FTLD disorders exemplified by progressive supranuclear palsy (PSP) are characterized by occasional tau accumulations in the cerebellum, hampering the application of CB-ref. The present study aimed to establish an optimal method for defining reference tissues on 18F-PM-PBB3-PET images of the AD and non-AD tauopathy brains. We developed a new algorithm to extract reference voxels with a low likelihood of containing tau deposits from gray matter (GM-ref) or white matter (WM-ref) by a bimodal fit to an individual, voxel-wise histogram of the radioligand retentions and applied it to 18F-PM-PBB3-PET data obtained from age-matched 40 healthy controls (HCs) and 23 AD, 40 PSP, and five other tau-positive FTLD patients. PET images acquired at 90-110 min after injection were averaged and co-registered to corresponding magnetic resonance imaging space. Subsequently, we generated standardized uptake value ratio (SUVR) images estimated by CB-ref, GM-ref and WM-ref respectively, and then compared the diagnostic performances. GM-ref and WM-ref covered a broad area in HCs and free of voxels located in regions known to bear high tau burdens in AD and PSP patients. GM-ref allowed the most robust separation of AD and PSP patients from HCs according to the area under the curves in receiver operating characteristic curve analyses. GM-ref also provided SUVR images with higher contrast than CB-ref in FTLD patients with suspected and confirmed corticobasal degeneration. The methodology for determining reference tissues as optimized here reinforces the accuracy of 18F-PM-PBB3-PET measurements of tau burdens in a wide range of neurodegenerative illnesses.
Transition to siblinghood causes substantial and long-lasting physiological stress reactions in wild bonobos
Authors: Behringer Verena , Berghänel Andreas , Lee Sean M. , Fruth Barbara , Hohmann Gottfried 
Published: February 2022

AbstractIn mammals with a slow ontogeny, the birth of a sibling marks a major developmental transition. Behavioral studies suggest that this event is stressful for the older offspring, but physiological evidence for this is lacking, and it remains unknown whether the birth of a sibling is stressful beyond mere weaning stress. Studying transition to siblinghood in wild bonobos, we investigated physiological changes in urinary cortisol (stress response), neopterin (cell-mediated immunity), and total triiodothyronine (metabolic rate), and related them to behavioral changes in mother-infant relationship and feeding (suckling, riding, proximity, body contact, independent foraging). With sibling’s birth, cortisol levels increased fivefold in the older offspring and remained elevated for seven months, independent of age. This was associated with diminished immunity but not with behavioral or metabolic changes. Our results indicate that transition to siblinghood is stressful beyond nutritional and social weaning and suggest that this effect is evolutionary old.
‘4-Aminoquinazoline-6, 7-diol’ derivatives for enhanced EGFR binding (as inhibitor) against Lung cancer
Authors: Maurya Pratibha Preeti 
Published: February 2022

ABSTRACTThe Epidermal growth factor receptor (EGFR) have been considered as potential targets for cancer therapy due to their role in regulating proliferation and survival of cancer cells. In the present study, the four ‘4-aminoquinazoline-6, 7-diol’ derivative molecules were selected to the theoretically investigate their inhibitory activity against EGFR protein. Molecules were evaluated on the basis of: (i) in-silico cytotoxic assay on human cancer cell lines expressing EGFR (A549 and A431), (ii) in-silico kinase assay, (iii) impact of molecular interaction on EGFR, (iv) molecular interaction stability, (v) inhibitory impact of molecules on combined expression of EGF-EGFR and (v) ADME observations. Studies were observed on the scale of two known EGFR inhibitors. In-silico cytotoxicity screening results demonstrated that the A431 lung cancer cell line was vulnerable to compound abc1-4. However, A549 cells were less sensitive to our designed molecules. From kinase inhibition assay results, compound abc1&2 were found to be an inhibitor against EGFR. According to the molecular interaction analysis, compounds abc1-4 performed in similar fashion of positive controls, acting at the catalytic site of EGFR. Altogether, these potent compounds, with compromised bioavailability, could likely be developed as a promising EGFR targeted drug(s) for cancer therapy.
Comparative transmission of SARS-CoV-2 Omicron (B.1.1.529) and Delta (B.1.617.2) variants and the impact of vaccination: national cohort study, England
Authors: Allen Hester , Tessier Elise , Turner Charlie , Anderson Charlotte , Blomquist Paula , Simons David , Løchen Alessandra , Jarvis Christopher I , Groves Natalie , Capelastegui Fernando , Flannagan Joe , Zaidi Asad , Chen Cong , Rawlinson Christopher , Hughes Gareth J. , Chudasama Dimple , Nash Sophie , Thelwall Simon , Lopez-Bernal Jamie , Dabrera Gavin , Charlett André , Kall Meaghan , Lamagni Theresa 
Published: February 2022

SummaryBackgroundThe SARS-CoV-2 Omicron variant (B.1.1.529) has rapidly replaced the Delta variant (B.1.617.2) to become dominant in England. This epidemiological study assessed differences in transmissibility between the Omicron and Delta using two methods and data sources.MethodsOmicron and Delta cases were identified through genomic sequencing, genotyping and S-gene target failure in England from 5-11 December 2021. Secondary attack rates for Omicron and Delta using named contacts and household clustering were calculated using national surveillance and contact tracing data. We used multivariable logistic regression was used to control for factors associated with transmission.FindingsAnalysis of contact tracing data identified elevated secondary attack rates for Omicron vs Delta in household (15.0% vs 10.8%) and non-household (8.2% vs 3.7%) settings. The proportion of index cases resulting in residential clustering was twice as high for Omicron (16.1%) compared to Delta (7.3%). Transmission was significantly less likely from cases, or in named contacts, in receipt of three compared to two vaccine doses in household settings, but less pronounced for Omicron (aRR 0.78 and 0.88) compared to Delta (aRR 0.62 and 0.68). In non-household settings, a similar reduction was observed for Delta cases and contacts (aRR 0.84 and 0.51) but only for Omicron contacts (aRR 0.76, 95% CI: 0.58-0.93) and not cases in receipt of three vs two doses (aRR 0.95, 0.77-1.16).InterpretationOur study identified increased risk of onward transmission of Omicron, consistent with its successful global displacement of Delta. We identified a reduced effectiveness of vaccination in lowering risk of transmission, a likely contributor for the rapid propagation of Omicron.FundingStudy funded by the UK Health Security Agency.
High-throughput profiling of natural acquired humoral immune response to a large panel of known and novel full length ectodomain P. falciparum merozoite vaccine candidates under reduced malaria transmission
Authors: Ndungu Duncan Ndegwa , Tuju James , Chepsat Emily , Mwai Rinter , Mwai Kennedy , Nyamako Lydia , Mosobo Moses , Deme Awa B. , Dieye Baba , Ndiaye Ibrahima Mbaye , Sy Mouhamad , Diallo Mamadou Alpha , Diedhiou Younous , Mbaye Amadou Moctar , Wirth Dyann , Ndiaye Daouda , Osier Faith , Bei Amy K. 
Published: February 2022

ABSTRACTDespite recent progress in the fight against malaria, it still remains a global health challenge necessitating development of intervention strategies. However, the search for malaria vaccine(s) has so far been very challenging. Multiple targets have been tested and so far only a few show promise with one having been endorsed by the WHO. In this study we explore the development of immunity in a low transmission setting, with very few documented re-infections, in order to understand the kinetics of the development and waning of immunity to current and novel blood-stage vaccine candidate antigens. To do this we performed a high-throughput measurement of natural acquired immunity against P. falciparum antigens utilizing a well-established micro-array platform based on the mammalian protein expression system. This large panel of known and novel recombinant full length ectodomain P. falciparum merozoite vaccine candidates were differently recognized by the immune system. Based on the overal spread of the data, some of these antigens induced the acquisition of high levels (1st tertile) of antibodies, among which included novel antigens such as PF3D7_1025300, PF3D7_1105800, PF3D7_1334400, PF3D7_0911300, PF3D7_1252300, PF3D7_1460600, PF3D7_1453100, PF3D7_0831400 and some induced low levels of antibodies (3rd tertile) while others induced moderate levels (4th tertile). In this longitudinal cohort with low level of malaria endemicity, acquisition of humoral immunity to these full length ectodomains P. falciparum antigens demonstrate different dynamics over-time, whereby it was either not acquired or if it was acquired it was either maintained or lost at different rates. These various identified novel antigens are potentially ideal candidates to be prioritized for further functional and or serological studies.