bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolution of β-lactamases and enzyme promiscuity
Authors: Fröhlich Christopher , Chen John Z , Gholipour Sevan , Erdogan Ayse N , Tokuriki Nobuhiko 
Published: May 2021

Abstract
β-Lactamases represent one of the most prevalent resistance mechanisms against β-lactam antibiotics. Beyond their clinical importance, they have also become key models in enzymology and evolutionary biochemistry. A global understanding of their evolution and sequence and functional diversity can therefore aid a wide set of different disciplines. Interestingly, β-lactamases have evolved multiple times from distinct evolutionary origins, with ancestries that reach back billions of years. It is therefore no surprise that these enzymes exhibit diverse structural features and enzymatic mechanisms. In this review, we provide a bird’s eye view on the evolution of β-lactamases within the two enzyme superfamilies—i.e. the penicillin-binding protein-like and metallo-β-lactamase superfamily—through phylogenetics. We further discuss potential evolutionary origins of each β-lactamase class by highlighting signs of evolutionary connections in protein functions between β-lactamases and other enzymes, especially cases of enzyme promiscuity.
Preoperative laboratory testing in elderly patients
Authors: Lee Kyung-Cheon , Lee Il-Ok 
Published: May 2021

Purpose of review
Preoperative testing in elderly patients is performed to examine the patient's current medical condition in the context of evaluating vulnerabilities and predicting postoperative complications to ensure that all functions recover before surgery. This review focused on preoperative laboratory tests in geriatric patients.

Recent findings
Preoperative complete blood count, electrolyte testing, and blood chemistry can predict postoperative complications. Preoperative elevated morning/evening salivary cortisol secretion ratio, C-reactive protein/albumin ratio (CAR), neutrophil/lymphocyte ratios, and preoperative decreased serum albumin level or 25-hydroxyvitamin D levels can predict postoperative cognitive dysfunction. Elevated brain-type natriuretic peptide or serum alkaline phosphatase levels can be biomarkers of major postoperative adverse cardiac events. Decreased preoperative estimated glomerular filtration rates and serum albumin levels can predict acute kidney injury. Hyponatremia, hypocalcemia, and low albumin/fibrinogen ratio predict postoperative complications. Hypoalbuminemia can predict surgical site infection or postoperative mortality after hip fracture surgery. A high CAR can predict anastomotic site leakage and is a risk factor for one-year mortality after hip surgery.

Summary
Preoperative laboratory testing helps predict postoperative adverse complications; thus, a plan of care can be initiated.
Clobetasol Compared With Fractionated Carbon Dioxide Laser for Lichen Sclerosus
Authors: Burkett Linda S. , Siddique Moiuri , Zeymo Alexander , Brunn Elizabeth A. , Gutman Robert E. , Park Amy J. , Iglesia Cheryl B. 
Published: May 2021

OBJECTIVE:
To compare 6-month safety and efficacy outcomes of fractionated CO2 laser (laser) with topical clobetasol propionate (steroid) for treatment of symptomatic vulvar lichen sclerosus.

METHODS:
We conducted a single-center randomized controlled trial that compared fractionated CO2 laser with steroid treatment for patients with biopsy-proven lichen sclerosus. Randomization was stratified by prior clobetasol propionate use. The primary outcome was mean change in Skindex-29 score at 6 months. A total sample size of 52 participants were recruited to detect a mean difference of 16 points on the Skindex-29 (SD±22) with 80% power, based on a one-sided two-sample t test with α=0.05, accounting for 10% attrition. Secondary outcomes included validated subjective and objective measures. Intention-to-treat, per protocol, and regression analysis based on prior steroid exposure were performed.

RESULTS:
From October 2015 to July 2018, 202 women were screened, 52 were randomized, and 51 completed a 6-month follow-up. No significant difference was found in baseline demographics, symptoms, and physician assessment scores. There was greater improvement in the Skindex-29 score in the laser arm at 6-months (10.9 point effect size, 95% CI 3.42–18.41; P=.007). Overall, 89% (23/27) of patients in the laser group rated symptoms as being “better or much better” compared with 62% (13/24) of patients in the steroid group, P=.07. More patients (81%, 21/27) were “satisfied or very satisfied” with laser treatment compared with steroid treatment (41%, 9/24); P=.01. After stratification for previous steroid use, the significant change of Skindex-29 score was only seen in the previously exposed group. There was one adverse event in each group: minor burning and blistering at the laser site and reactivation of genital herpes 1 week after starting steroid.

CONCLUSION:
Fractionated CO2 laser treatment showed significant improvement in subjective symptoms and objective measures compared with clobetasol propionate, without serious safety or adverse events at 6 months.

CLINICAL TRIAL REGISTRATION:
ClinicalTrials.gov, NCT02573883.
Chorioamnionitis and Risk for Maternal and Neonatal Sepsis
Authors: Beck Celeste , Gallagher Kelly , Taylor Leigh A. , Goldstein Jeffery A. , Mithal Leena B. , Gernand Alison D. 
Published: May 2021

OBJECTIVE:
To estimate the risk of maternal and neonatal sepsis associated with chorioamnionitis.

DATA SOURCES:
PubMed, BIOSIS, and ClinicalTrials.gov databases were systematically searched for full-text articles in English from inception until May 11, 2020.

METHODS OF STUDY SELECTION:
We screened 1,251 studies. Randomized controlled trials, case-control, or cohort studies quantifying a relationship between chorioamnionitis and sepsis in mothers (postpartum) or neonates born at greater than 22 weeks of gestation were eligible. Studies were grouped for meta-analyses according to exposures of histologic or clinical chorioamnionitis and outcomes of maternal or neonatal sepsis.

TABULATION, INTEGRATION, AND RESULTS:
One hundred three studies were included, and 55 met criteria for meta-analysis (39 studies of preterm neonates, 10 studies of general populations of preterm and term neonates, and six studies of late preterm and term neonates). Study details and quantitative data were abstracted. Random-effects models were used to generate pooled odds ratios (ORs); most studies only reported unadjusted results. Histologic chorioamnionitis was associated with confirmed and any early-onset neonatal sepsis (unadjusted pooled ORs 4.42 [95% CI 2.68–7.29] and 5.88 [95% CI 3.68–9.41], respectively). Clinical chorioamnionitis was also associated with confirmed and any early-onset neonatal sepsis (unadjusted pooled ORs 6.82 [95% CI 4.93–9.45] and 3.90 [95% CI 2.74–5.55], respectively). Additionally, histologic and clinical chorioamnionitis were each associated with higher odds of late-onset sepsis in preterm neonates. Confirmed sepsis incidence was 7% (early-onset) and 22% (late-onset) for histologic and 6% (early-onset) and 26% (late-onset) for clinical chorioamnionitis-exposed neonates. Three studies evaluated chorioamnionitis and maternal sepsis and were inconclusive.

CONCLUSION:
Both histologic and clinical chorioamnionitis were associated with early- and late-onset sepsis in neonates. Overall, our findings support current guidelines for preventative neonatal care. There was insufficient evidence to determine the association between chorioamnionitis and maternal sepsis.

SYSTEMATIC REVIEW REGISTRATION:
PROSPERO, CRD42020156812.
Performance and Diagnostic Value of Genome-Wide Noninvasive Prenatal Testing in Multiple Gestations
Authors: van Riel Margot , Brison Nathalie , Baetens Machteld , Blaumeiser Bettina , Boemer François , Bourlard Laura , Bulk Saskia , De Leener Anne , Désir Julie , Devriendt Koenraad , Dheedene Annelies , Duquenne Armelle , Fieremans Nathalie , Fieuw Annelies , Gatot Jean-Stéphane , Grisart Bernard , Janssens Sandra , Khudashvili Naïri , Lannoo Lore , Marichal Axel , Meunier Colombine , Palmeira Leonor , Parijs Ilse , Pichon Bruno , Roets Ellen , Sammels Eva , Smits Guillaume , Suenaert Marion , Sznajer Yves , Van den Bogaert Kris , Vancoillie Leen , Vandeputte Lotte , Vantroys Elise , Vermeesch Joris Robert , Janssens Katrien 
Published: May 2021

OBJECTIVE:To evaluate the accuracy and diagnostic value of genome-wide noninvasive prenatal testing (NIPT) for the detection of fetal aneuploidies in multiple gestations, with a focus on dichorionic–diamniotic twin pregnancies.METHODS:We performed a retrospective cohort study including data from pregnant women with a twin or higher-order gestation who underwent genome-wide NIPT at one of the eight Belgian genetic centers between November 1, 2013, and March 1, 2020. Chorionicity and amnionicity were determined by ultrasonography. Follow-up invasive testing was carried out in the event of positive NIPT results. Sensitivity and specificity were calculated for the detection of trisomy 21, 18, and 13 in the dichorionic–diamniotic twin cohort.RESULTS:Unique NIPT analyses were performed for 4,150 pregnant women with a multiple gestation and an additional 767 with vanishing gestations. The failure rate in multiple gestations excluding vanishing gestations ranged from 0% to 11.7% among the different genetic centers. Overall, the failure rate was 4.8%, which could be reduced to 1.2% after single resampling. There were no common fetal trisomies detected among the 86 monochorionic–monoamniotic and 25 triplet cases. Two monochorionic–diamniotic twins had an NIPT result indicative of a trisomy 21, which was confirmed in both fetuses. Among 2,716 dichorionic–diamniotic twin gestations, a sensitivity of 100% (95% CI 74.12–100%) and a specificity of 100% (95% CI 99.86–100%) was reached for trisomy 21 (n=12). For trisomy 18 (n=3), the respective values were 75% (95% CI 30.06–95.44%) sensitivity and 100% (95% CI 99.86–100%) specificity, and for trisomy 13 (n=2), 100% (95% CI 20.65–100%) sensitivity and 99.96% (95% CI 99.79–99.99%) specificity. In the vanishing gestation group, 28 NIPT results were positive for trisomy 21, 18, or 13, with only five confirmed trisomies.CONCLUSION:Genome-wide NIPT performed accurately for detection of aneuploidy in dichorionic–diamniotic twin gestations.
Delivery Mode After Manual Rotation of Occiput Posterior Fetal Positions
Authors: Verhaeghe Caroline , Corroenne Romain , Spiers Andrew , Descamps Philippe , Gascoin Géraldine , Bouet Pierre-Emmanuel , Parot-Schinkel Elsa , Legendre Guillaume 
Published: May 2021

OBJECTIVE:
To evaluate whether manual rotation of fetuses in occiput posterior positions at full dilation increases the rate of spontaneous vaginal delivery.

METHODS:
In an open, single-center, randomized controlled trial, patients with a term, singleton gestation, epidural analgesia, and ultrasonogram-confirmed occiput posterior position at the start of the second stage of labor were randomized to either manual rotation or expectant management. Our primary endpoint was the rate of spontaneous vaginal delivery. Secondary endpoints were operative vaginal delivery, cesarean delivery, and maternal and neonatal morbidity. Analyses were based on an intention-to-treat method. A sample size of 107 patients per group (n=214) was planned to detect a 20% increase in the percent of patients with a spontaneous vaginal delivery (assuming 60% without manual rotation vs 80% with manual rotation) with 90% power and alpha of 0.05.

RESULTS:
Between February 2017 and January 2020, 236 patients were randomized to either manual rotation (n=117) or expectant management (n=119). The success rate of the manual rotation maneuver, defined by conversion to an anterior position as confirmed by ultrasonogram, was 68%. The rate of the primary endpoint did not differ between the groups (58.1% in manual rotation group vs 59.7% in expectant management group (risk difference −1.6; 95% CI −14.1 to 11.0). Manual rotation did not decrease the rate of operative vaginal delivery (29.9% in manual rotation group vs 33.6% in expectant management group (risk difference −3.7; 95% CI −16.6 to 8.2) nor the rate of cesarean delivery (12.0% in manual rotation group vs 6.7% in expectant management group (risk difference 5.3; 95% CI −2.2 to 12.6). Maternal and neonatal morbidity was also similar across the two groups.

CONCLUSION:
Manual rotation of occiput posterior positions at the start of second stage of labor does not increase the rate of vaginal delivery without instrumental assistance.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT03009435.
Differentiating Acute Rejection From Preeclampsia After Kidney Transplantation
Authors: Yin Ophelia , Kallapur Aneesh , Coscia Lisa , Constantinescu Serban , Moritz Michael , Afshar Yalda 
Published: May 2021

OBJECTIVE:
To evaluate the clinical and laboratory characteristics in pregnancy that differentiate preeclampsia from acute renal allograft rejection and to investigate the maternal, neonatal, and graft sequelae of these diagnoses.

METHODS:
We conducted a retrospective case-controlled registry study of data abstracted from Transplant Pregnancy Registry International deliveries between 1968 and 2019. All adult kidney transplant recipients with singleton pregnancies of at least 20 weeks of gestation were included. Acute rejection was biopsy proven and preeclampsia was diagnosed based on contemporary criteria. Variables were compared using χ2, Fisher exact, and Wilcoxon rank sum tests as appropriate. Multivariable linear regression was used to analyze preterm birth. Kaplan-Meier curves with log-rank test and Cox proportional hazards model were used to compare graft loss over time.

RESULTS:
There were 26 pregnant women with biopsy-confirmed acute rejection who were matched by the year they conceived to 78 pregnant women with preeclampsia. Recipients with acute rejection had elevated peripartum serum creatinine levels (73% vs 14%, P<.001), with median intrapartum creatinine of 3.90 compared with 1.15 mg/dL (P<.001). Conversely, only patients with preeclampsia had a significant increase in proteinuria from baseline. Although there were no significant differences in maternal outcomes, graft loss within 2 years postpartum (42% vs 10%) and long-term graft loss (73% vs 35%) were significantly increased in recipients who experienced acute rejection (P<.001 for both). The frequency of delivery before 32 weeks of gestation was 53% with acute rejection and 20% with preeclampsia. After controlling for hypertension and immunosuppressant use, acute rejection was associated with higher frequency of delivery at less than 32 weeks of gestation (adjusted odds ratio 4.04, 95% CI 1.10–15.2).

CONCLUSION:
In pregnancy, acute rejection is associated with higher creatinine levels, and preeclampsia is associated with increased proteinuria. Acute rejection in pregnancy carries a risk of prematurity and graft loss beyond that of preeclampsia for kidney transplant recipients.

FUNDING SOURCE:
The Transplant Pregnancy Registry International is supported in part by an educational grant from Veloxis Pharmaceuticals.
Surgical Management of Symptomatic Apical Pelvic Organ Prolapse
Authors: Larouche Maryse , Belzile Eric , Geoffrion Roxana 
Published: May 2021

OBJECTIVE:
To systematically review objective and subjective success and complications of apical suspensions for symptomatic uterine or vaginal vault pelvic organ prolapse (POP).

DATA SOURCES:
MEDLINE, CENTRAL, ClinicalTrials.gov, and EMBASE (2002–2019) were searched using multiple terms for apical POP surgeries, including comparative studies in French and English.

METHODS OF STUDY SELECTION:
From 2,665 records, we included randomized controlled trials and comparative studies of interventions with or without hysterectomy, including abdominal apical reconstruction through open, laparoscopic, or robotic approaches and vaginal apical reconstructions. Repairs using transvaginal mesh, off-the-market products, procedures without apical suspension, and follow-up less than 6 months were excluded.

TABULATION, INTEGRATION, AND RESULTS:
Relative risk (RR) was used to estimate the effect of surgical procedure on each outcome. For each outcome and comparison, a meta-analysis was conducted to pool the RRs when possible. Meta-regression and bias tests were performed when appropriate. The GRADE (Grades for Recommendation, Assessment, Development and Evaluation) system for quality rating and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) reporting were used. Sixty-two articles were included in the review (N=22,792) and 50 studies in the meta-analyses. There was heterogeneity in study quality, techniques used, and outcomes reported. Median follow-up was 1–5 years. Vaginal suspensions showed higher risk of overall and apical anatomic recurrence compared with sacrocolpopexy (RR 1.82, 95% CI 1.22–2.74 and RR 2.70, 95% CI 1.33–5.50) (moderate), whereas minimally invasive sacrocolpopexy showed less overall and posterior anatomic recurrence compared with open sacrocolpopexy (RR 0.59, 95% CI 0.47–0.75 and RR 0.59, 95% CI 0.44–0.80, respectively) (low). Different vaginal approaches, and hysterectomy and suspension compared with hysteropexy had similar anatomic success. Subjective POP recurrence, reintervention for POP recurrence and complications were similar between most procedures.

CONCLUSION:
Despite variations in anatomic outcomes, subjective outcomes and complications were similar for apical POP procedures at 1–5 years. Standardization of outcome reporting and comparative studies with longer follow-up are urgently needed.

SYSTEMATIC REVIEW REGISTRATION:
PROSPERO, CRD42019133869.
Preoperative Decision to Perform Portal Vein Resection Improves Survival in Patients With Resectable Pancreatic Head Cancer Adjacent to Portal Vein
Authors: Terasawa Muga , Mise Yoshihiro , Yoshioka Ryuji , Oba Atsushi , Ono Yoshihiro , Inoue Yosuke , Imamura Hiroshi , Hiromichi Ito , Takahashi Yu , Kawasaki Seiji , Saiura Akio 
Published: May 2021

Objective:
We hypothesized that preoperatively planned portal vein resection (PVR), which prevents from approaching tumors, improves survival in patients with resectable pancreatic head cancer adjacent to the portal vein (PhC-PV).

Summary:
The decision to perform PVR is difficult in patients with resectable PhC-PV.

Methods:
This is a retrospective, bi-institutional study of patients undergoing pancreatoduodenectomy (PD) for resectable PhC-PV from 2009 to 2018. We compared clinical data of patients who underwent PD with preoperatively planned PVR (planned PVR group) and those who underwent conventional PD (cPD) in which decision to perform PVR was made intraoperatively (cPD group).

Results:
Among the study population of 176 patients, 53 patients (30.1%) underwent PD with planned PVR. The remaining 123 patients (69.9%) underwent cPD. Tumor characteristics were similar between the 2 groups. Operation time and major complication rates did not differ between the 2 groups. The local recurrence rate of patients in the planned PVR group (28.3%) was lower than that of the cPD group (44.7%; P = 0.041). Median overall survival (OS) was longer in the planned PVR group than in the cPD group (32 vs 27 months; P = 0.011). Multivariate analysis revealed that having undergone planned PVR was an independent factor for favorable OS (hazard ratio = 1.65; 95% confidence interval = 1.08–2.61; P = 0.021).

Conclusions:
The preoperative decision to perform PVR improves survival by enhancing local control of resectable PhC-PV.
Construct Validity and Item Response Theory Analysis of the PROMIS-29 v2.0 in Recipients of Lumbar Spine Surgery
Authors: Cook Chad E. , Rethorn Zachary D. , Chiarotto Alessandro , Garcia Alessandra N. , Gottfried Oren 
Published: May 2021

Study Design.
Observational cohort design involving measurement property assessment.

Objectives.
The aim of this study was to assess construct validity through hypothesis testing and to examine reliability and discrimination of the PROMIS-29 v2.0 using item response theory (IRT) analyses.

Summary of Background Data.
Patient-Reported Outcomes Measurement Information System (PROMIS) 29.0 version 2.0 includes 28 questions for the seven domains of Physical function, Anxiety, Depression, Fatigue, Sleep disturbance, Social role, and Pain interference, and one item related to pain intensity. To date, the tool has not been tested for construct validity for selected concepts, nor has it been evaluated using IRT in a population of spine surgery recipients.

Methods.
Using the Quality Outcomes Dataset lumbar registry, we evaluated the construct validity of the PROMIS-29 v2.0 against pain intensity measures for back and leg, the Oswestry Disability Index, the EQ5D 3L-visual analog scale (quality of life) and proxy measures of activities, mobility and self-care. IRT was used to test PROMIS-29 v2.0 assumptions and fit.

Results.
The sample included 652 surgery recipients (mean age = 60.1, SD = 14.0) who had a high level of baseline disability. Hypothesis testing confirmed direction and magnitude of correlation between the PROMIS and legacy measures in 10 of the 12 hypotheses. IRT identified three misfit items, but otherwise adequate scale reliability and unidimensionality.

Conclusion.
The PROMIS-29 v2.0 measures several different constructs pertinent to a patient's health and recovery during spine surgery. We feel that the PROMIS-29 v2.0 tool is a useful and effective outcome measure for populations who receive spine surgery.

Level of Evidence: 4
Cyclic Tensile Stress to Rat Thoracolumbar Ligamentum Flavum Inducing the Ossification of Ligamentum Flavum
Authors: Zhao Yin , Yuan Bo , Cheng Li , Zhou Shengyuan , Tang Yifan , Zhang Zhichao , Sun Yanqing , Xu Zheng , Li Fengning , Liao Xinyuan , Chen Xiongsheng 
Published: May 2021

Study Design.
Western blot, reverse transcription-polymerase chain reaction (RT-PCR), radiological, and histological analyses of the rat ossification of ligamentum flavum (OLF) induced by cyclic tensile stress.

Objective.
The aim of this study was to induce the OLF using cyclic tensile stress to rat thoracolumbar ligamentum flavum, and to investigate the possible molecular mechanism of tension-induced OLF.

Summary of Background Data.
Tensile stress has been considered as an important factor leading to the OLF. So far, however, no OLF induced by tension has been reported.

Methods.
Forty rats were randomly divided into five equal groups. For control groups, the blank and anesthesia groups were not subjected to tension. For experimental groups, the 4-, 8-, and 12-week groups were subjected to cyclic tensile stress of ligamentum flavum after abdominal anesthesia for 4 weeks, 8 weeks, and 12 weeks, respectively, using an original stress apparatus for rats. The radiological and morphological changes of rat spine, as well as the protein and mRNA expressions of CD44, bone morphogenetic protein-2 (BMP-2), integrin β3, collagen protein type I (COL1), osteopontin (OPN), runt-related transcription factor 2 (RUNX-2), and vascular endothelial growth factor (VEGF), were concerned.

Results.
The micro-CT showed OLF in the 4-, 8-, and 12-week group. The axial maximum occupied area of ossifications was 1.42 mm2, 3.35 mm2, and 7.28 mm2, respectively. In histopathology, chondrocytes proliferated in the experimental model; woven bone arose in the 8- and 12-week groups, and was more noticeable in the 12-week group. According to western blot and RT-PCR, the expressions of seven osteogenesis-related molecules were all increased in three experimental groups.

Conclusion.
Cyclic tensile stress to the ligamentum flavum in rats can induce the OLF, and the longer the duration, the more visible the osteogenesis. The upregulation and synergism of osteogenesis-related molecules may contribute to the OLF induced by tensile stress.

Level of Evidence: N/A