bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential associations of APOE-ε2 and APOE-ε4 alleles with PET-measured amyloid-β and tau deposition in older individuals without dementia
Authors: Salvadó Gemma , Grothe Michel J. , Groot Colin , Moscoso Alexis , Schöll Michael , Gispert Juan Domingo , Ossenkoppele Rik ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: February 2021

Abstract
Purpose
To examine associations between the APOE-ε2 and APOE-ε4 alleles and core Alzheimer’s disease (AD) pathological hallmarks as measured by amyloid-β (Aβ) and tau PET in older individuals without dementia.

Methods
We analyzed data from 462 ADNI participants without dementia who underwent Aβ ([18F]florbetapir or [18F]florbetaben) and tau ([18F]flortaucipir) PET, structural MRI, and cognitive testing. Employing APOE-ε3 homozygotes as the reference group, associations between APOE-ε2 and APOE-ε4 carriership with global Aβ PET and regional tau PET measures (entorhinal cortex (ERC), inferior temporal cortex, and Braak-V/VI neocortical composite regions) were investigated using linear regression models. In a subset of 156 participants, we also investigated associations between APOE genotype and regional tau accumulation over time using linear mixed models. Finally, we assessed whether Aβ mediated the cross-sectional and longitudinal associations between APOE genotype and tau.

Results
Compared to APOE-ε3 homozygotes, APOE-ε2 carriers had lower global Aβ burden (βstd [95% confidence interval (CI)]: − 0.31 [− 0.45, − 0.16], p = 0.034) but did not differ on regional tau burden or tau accumulation over time. APOE-ε4 participants showed higher Aβ (βstd [95%CI]: 0.64 [0.42, 0.82], p < 0.001) and tau burden (βstd range: 0.27-0.51, all p < 0.006). In mediation analyses, APOE-ε4 only retained an Aβ-independent effect on tau in the ERC. APOE-ε4 showed a trend towards increased tau accumulation over time in Braak-V/VI compared to APOE-ε3 homozygotes (βstd [95%CI]: 0.10 [− 0.02, 0.18], p = 0.11), and this association was fully mediated by baseline Aβ.

Conclusion
Our data suggest that the established protective effect of the APOE-ε2 allele against developing clinical AD is primarily linked to resistance against Aβ deposition rather than tau pathology.
Effective dissection for rectal cancer with lateral lymph node metastasis based on prognostic factors and recurrence type
Authors: Morohashi Hajime , Sakamoto Yoshiyuki , Miura Takuya , Ichinohe Daichi , Umemura Kotaro , Akaishi Takanobu , Sato Kentaro , Kuwata Daisuke , Yamazaki Keisuke , Wakiya Taiichi , Hakamada Kenichi 
Published: February 2021

Abstract
Purpose
There are no reports showing the significance and effective range of dissection for patients with lateral lymph node metastasis (LLNM). This study aimed to investigate the indications for lateral lymph node dissection (LLND) in patients with LLNM based on prognostic factors and recurrence types.

Methods
We reviewed 379 patients with advanced rectal cancer who were treated with total mesorectal excision plus LLND. We analyzed background factors and survival times of patients who had LLNM to determine prognostic factors and recurrence types.

Results
Pathological LLNM occurred in 44 (11.6%). Among patients with LLNM, the predictors of poor prognoses, according to univariate analysis, were > 3 node metastases, the presence of node metastasis on both sides, and spreading beyond the internal iliac lymph nodes. Moreover, LLNM beyond the internal iliac region was found to be an independent prognostic risk factor. Twenty-eight of the 44 patients with lateral lymph node metastasis (64%) relapsed, 22 of whom had distant metastases and 11 of whom experienced local recurrences. Among the latter group, nine (20%) and two (5%) had recurrences in the central and lateral pelvis, respectively.

Conclusion
The therapeutic benefit of resection was high, especially in patients with ≤ 3 positive lateral lymph nodes, one-sided bilateral lymph node areas, and positive nodes localized near the internal iliac artery.
From forest to fragment: compositional differences inside coastal forest moth assemblages and their environmental correlates
Authors: Uhl Britta , Wölfling Mirko , Fiedler Konrad 
Published: February 2021

AbstractPatterns of β-diversity can provide insight into forces shaping community assembly. We analyzed species-rich insect assemblages in two reserve fragments that had once been part of one contiguous Mediterranean coastal pine forest. Local environments are still similar across both fragments, but their landscape context differs strongly, with one surrounded by intense agricultural land, while the other neighbors the urbanized area of Ravenna. Using 23,870 light-trap records of 392 moth species, and multiple local and landscape metrics, we compared the relative importance of habitat- versus landscape-scale environmental factors for shaping small-scale variation in differentiation and proportional insect β-diversity across 30 sites per reserve. Moth assemblage composition differed substantially between fragments, most likely due to ecological drift and landscape-scale variation. For proportional β-diversity, especially local forest structure was important. At well-developed forest sites, additive homogenization could be observed, whereas the lack of typical forest species at dry, dense, and younger forest sites increased species turnover (subtractive heterogenization). For differentiation β-diversity, local and landscape-scale factors were equally important in both reserves. At the landscape-scale (500 m radius around light-trapping sites) the proximity to urban areas and the fraction of human-altered land were most important. At the habitat scale, gradients in soil humidity, nutrient levels and forest structure mattered most, whereas plant diversity had very little explanatory power. Overall, landscape-scale anthropogenic alterations had major effects on moth communities inside the two conservation areas. Yet, even for these parts of one formerly contiguous forest trajectories in community change were remarkably idiosyncratic.
Routine intraoperative cholangiography during laparoscopic cholecystectomy: application of the 2016 WSES guidelines for predicting choledocholithiasis
Authors: Lai Hui-Ying , Tsai Kuei-Yen , Chen Hsin-An 
Published: February 2021

Abstract
Background
Routine use of intraoperative cholangiography (IOC) during laparoscopic cholecystectomy (LC) for detecting common bile duct stones remains controversial. The 2016 World Society of Emergency Surgery (WSES) guidelines on acute calculous cholecystitis proposed a risk stratification for choledocholithiasis. Our present study aimed to (1) examine the findings of common bile duct (CBD) stones in patients underwent LC with routine use of IOC, and (2) validate the 2016 WSES risk classes for predicting choledocholithiasis.

Methods
All patients had LC with IOC routinely performed from November 2012 to December 2017 were reviewed retrospectively. Patients were classified into high-, intermediate-, and low-risk groups based on the 2016 WSES risk classes with modification.

Results
A total of 990 patients with LC and routine IOC were enrolled. CBD stones were detected in 197 (19.9%) patients. The rate of CBD stone detected in low-, intermediate-, high-risk groups were 0%, 14.2%, and 89.6%, respectively. Predictors as following: evidence of CBD stones on abdominal ultrasound or computed tomography, CBD diameter > 6 mm, total bilirubin > 4 mg/dL, bilirubin level = 1.8–4 mg/dL, abnormal liver biochemical test result other than bilirubin, presence of clinical gallstone pancreatitis had statistical significance between patients with and without CBD stones. Major bile duct injury was found in 4 patients (0.4%). All 4 patients had uneventful recovery after repair surgery.

Conclusions
Based on our study results, the 2016 WSES risk classes for choledocholithiasis could be an effective approach for predicting the risk of choledocholithiasis. Considering its advantages for detecting CBD stones and biliary injuries, the routine use of IOC is still suggested.
Laparoscopic negative appendectomy during pregnancy is associated with adverse neonatal outcome
Authors: Rottenstreich Misgav , Tankel James , Vilk Ayalon Naama , Rotem Reut , Yellinek Shlomo , Khatib Fayez , Grisaru-Granovsky Sorina 
Published: February 2021

Abstract
Background
The impact on pregnancy of laparoscopy for acute appendicitis is well documented. However, with an accurate pre-operative diagnosis being more challenging in pregnant patients, the incidence of a negative appendectomy (NA) is higher in this cohort. The aim of this study was to evaluate the maternal and neonatal implications of a NA during pregnancy.

Methods
A single center retrospective study between 2004 and 2019 was performed. Pregnant women who underwent laparoscopic appendectomy for suspected appendicitis were identified from which those who had a pathologically normal appendix were selected. The maternal and neonatal outcome of this group were compared with a matched control group of pregnant women who underwent diagnostic laparoscopy for a presumed ovarian torsion in whom no further surgical intervention was performed. Multivariate regression analysis was performed to explore factors that gestational size.

Results
Of the 225 pregnant women who underwent laparoscopy appendectomy, a NA was performed in 33 (14.7%). These were compared with 50 pregnant women in the diagnostic laparoscopy group. The former was characterized by higher rate of nulliparity and later gestational age at the time of the surgery (17.8 ± 7.5 vs 11.3 ± 6.3, p < 0.001). Whilst the rate of maternal complications during pregnancy were similar between the groups, NA was associated with significantly lower neonatal birthweights (2733.9 ± 731.1 vs 3200.7 ± 458.5 g, p = 0.002) and a significantly higher risk of small for gestational age (SGA) infants (OR 5.6, 95% CI 1.02–30.9).

Conclusions
Performing a NA during pregnancy is an indicator for perioperative counseling and antenatal follow up.
Associated characteristics and treatment outcomes of medication-related osteonecrosis of the jaw in patients receiving denosumab or zoledronic acid for bone metastases
Authors: Ikesue Hiroaki , Mouri Moe , Tomita Hideaki , Hirabatake Masaki , Ikemura Mai , Muroi Nobuyuki , Yamamoto Shinsuke , Takenobu Toshihiko , Tomii Keisuke , Kawakita Mutsushi , Katoh Hironori , Ishikawa Takayuki , Yasui Hisateru , Hashida Tohru 
Published: February 2021

Abstract
Purpose
This study aimed to evaluate the association between clinical characteristics and development of medication-related osteonecrosis of the jaw (MRONJ) in patients who underwent dental examinations before the initiation of treatment with denosumab or zoledronic acid, which are bone-modifying agents (BMAs), for bone metastases. Additionally, the clinical outcomes of patients who developed MRONJ were evaluated along with the time to resolution of MRONJ.

Methods
The medical charts of patients with cancer who received denosumab or zoledronic acid for bone metastases between January 2012 and September 2016 were retrospectively reviewed. Patients were excluded if they did not undergo a dental examination at baseline.

Results
Among the 374 included patients, 34 (9.1%) developed MRONJ. The incidence of MRONJ was significantly higher in the denosumab group than in the zoledronic acid (27/215 [12.6%] vs 7/159 [4.4%], P = 0.006) group. Multivariate Cox proportional hazards regression analysis revealed that denosumab treatment, older age, and tooth extraction before and after starting BMA treatments were significantly associated with developing MRONJ. The time to resolution of MRONJ was significantly shorter for patients who received denosumab (median 26.8 months) than for those who received zoledronic acid (median not reached; P = 0.024).

Conclusion
The results of this study suggest that treatment with denosumab, age > 65 years, and tooth extraction before and after starting BMA treatments are significantly associated with developing MRONJ in patients undergoing treatment for bone metastases. However, MRONJ caused by denosumab resolves faster than that caused by zoledronic acid.
New-onset seizures after cranioplasty—a different view on a putatively frequently observed phenomenon
Authors: Hirschmann Dorian , Kranawetter Beate , Tomschik Matthias , Wais Jonathan , Winter Fabian , Frischer Josa M. , Millesi Matthias , Herta Johannes , Roessler Karl , Dorfer Christian 
Published: February 2021

Abstract
Background
New-onset seizures after cranioplasty (NOSAC) are reported to be a frequent complication of cranioplasty (CP) after decompressive hemicraniectomy (DHC). There are considerable differences in the incidence of NOSAC and contradictory data about presumed risk factors in the literature. We suggest NOSAC to be a consequence of patients’ initial condition which led to DHC, rather than a complication of subsequent CP. We conducted a retrospective analysis to verify our hypothesis.

Methods
The medical records of all patients ≥ 18 years who underwent CP between 2002 and 2017 at our institution were evaluated including incidence of seizures, time of seizure onset, and presumed risk factors. Indication for DHC, type of implant used, timing of CP, patient age, presence of a ventriculoperitoneal shunt (VP shunt), and postoperative complications were compared between patients with and without NOSAC.

Results
A total of 302 patients underwent CP between 2002 and 2017, 276 of whom were included in the outcome analysis and the incidence of NOSAC was 23.2%. Although time between DHC and CP differed significantly between DHC indication groups, time between DHC and seizure onset did not differ, suggesting the occurrence of seizures to be independent of the procedure of CP. Time of follow-up was the only factor associated with the occurrence of NOSAC.

Conclusion
New-onset seizures may be a consequence of the initial condition leading to DHC rather than of CP itself. Time of follow-up seems to play a major role in detection of new-onset seizures.
Surgical management in submucous cleft palate patients
Authors: Smarius B. J. A. , Guillaume C. H. A. L. , Slegers J. , Mink van der Molen A. B. , Breugem C. C. 
Published: February 2021

AbstractObjectivesThe submucous cleft palate (SMCP) is considered to be the most subtle type of cleft palate. Early detection is important to allow on time intervention by speech therapy and/or surgical repair before the children already develop compensatory speech mechanisms. The purpose of this study was to investigate at what time children with a SMCP present, to determine when children are operated, and to analyze the postoperative outcomes for in SMCP children.Patient and methodsMedical records from 766 individuals registered in the cleft registry in the Wilhelmina’s Children’s’ Hospital, Utrecht, were retrospectively reviewed. Inclusion criteria were children diagnosed with SMCP. The following data were collected: age at diagnosis, physical examination, age at surgery, surgical technique, speech therapy pre- and post-surgery, otitis media, secondary cleft surgery, family history, syndromes, and other anomalies.ResultsIn total, 56 SMCP children were identified. The mean age of diagnosis was 44.0 months (range 0–150, SD = 37.0). In 48 children (85.7%), surgical intervention was performed (Furlow plasty, intravelar veloplasty, pharyngoplasty, or Furlow combined with buccal flap).ConclusionThis retrospective study reconfirms that SMCP often presents late, even in a country with a modern healthcare system and adequate follow-up of all newborns by the so-called youth doctors in “children’s healthcare centers” up to the age of 4 years old. Almost 86% of patients ultimately needed palate surgery when SMCP was suspected.Clinical relevanceAny child presenting with repeated episodes of otitis media, nasal regurgitation, or speech difficulties should have prompt consideration for SMCP as diagnosis.
RCT on the effectiveness of the intraligamentary anesthesia and inferior alveolar nerve block on pain during dental treatment
Authors: Youssef Bahaa R. , Söhnel Andreas , Welk Alexander , Abudrya Mohamed H. , Baider Mohamed , Alkilzy Mohammad , Splieth Christian 
Published: February 2021

AbstractObjectiveTo compare the effectiveness and complications of intraligamentary anesthesia (ILA) with conventional inferior alveolar nerve block (IANB) during injection and dental treatment of mandibular posterior teeth.Materials and methodsIn this randomized, prospective clinical trial, 72 patients (39 males, 33 females), scheduled for dental treatment of mandibular posterior teeth, were randomly allocated to ILA group (n = 35) received ILA injection or IANB group (n = 37) received the conventional IANB. Our primary outcome was to assess pain and stress (discomfort) during the injection and dental treatment, using the numeric rating scale (NRS) from 0 to 10 (0 = no pain, 10= the worst pain imaginable), whereas recording 24-h postoperative complications was our secondary outcomes.ResultsPatients in ILA group reported significantly less pain during injection when compared with IANB group (p = 0.03), while pain during dental treatment was similar in both groups (p = 0.2). Patients in both groups also reported similar law values of discomfort during treatment (p = 0.7). Although no signs of nerve contact or any other postoperative complications were observed, five patients in IANB group (none in ILA group) reported temporary irritations.ConclusionThis study showed equivalent effectiveness of both intraligamentary anesthesia and conventional inferior alveolar nerve block, for pain control during routine dental treatment of mandibular posterior teeth. Nevertheless, ILA showed significantly less pain during injection. No major postoperative complications in both groups were observed.Clinical relevanceILA could be considered as an effective alternative for routine dental treatment.Trial registrationNCT04563351
Efficacy and acceptability of the S1P receptor in the treatment of multiple sclerosis: a meta-analysis
Authors: Tong Jingyi , Zou Qin , Chen Yongmin , Liao Xiaoping , Chen Rong , Ma Lin , Zhang Daqi , Li Qifu 
Published: February 2021

Abstract
Background and objective
Sphingosine-1-phosphate (S1P) receptors are extensively used in the treatment of multiple sclerosis (MS). However, the optimal therapeutic role of S1P in MS patients has still remained elusive. This network meta-analysis (NMA) systematically evaluated the efficacy and acceptability of S1P receptors, as disease-modifying drugs, in the treatment of patients with MS, so as to find out the most appropriate therapeutic strategy and provide a reliable basis for the prescription of S1P drugs for patients with MS.

Methods
We conducted a systematic review and NMA to compare the efficacy and acceptability of S1P receptors for treating MS patients. Randomized controlled trials (RCTs), which were published until May 2020, were retrieved from the PubMed, Cochrane Library, Embase, and ClinicalTrials.gov databases. The primary outcome in this study was the treatment efficacy for the S1P receptor for MS patients, in terms of decrease in annualized relapse rate. The secondary outcomes were adverse events leading to discontinuation of a study, such as an unfavorable or unintended sign/symptom. Outcomes were appraised using a random effects model expressed as standardized mean differences (SMDs) and risk ratios (RRs) with 95% confidence intervals (CIs), respectively, and were ranked using surface under the cumulative ranking curve (SUCRA) probabilities for hierarchical clustering of interventions.

Results
A total of 13 RCTS were included, which enrolled 10,554 patients. The results of NMA showed that Fingolimod, Laquinimod, Siponimod, Ozanimod, Amiselimod, and Ponesimod were superior to placebo in terms of reducing the annualized relapse rate of MS patients. Regarding efficacy, the best and worst treatments were Amiselimod (0.4 mg; SUCRA 8.1%) and placebo (SUCRA 90.5%), respectively. As for acceptability, the best and worst interventions were Ozanimod (1 mg; SUCRA 20.4%) and Ponesimod (40 mg; SUCRA 96.0%), respectively. The comparison-adjusted funnel plots of annualized relapse rate and side effects in the included studies revealed that there was no significant funnel plot asymmetry

Conclusions
This NMA indicated that Amiselimod (0.4 mg) is the most effective treatment strategy as a S1P receptor for MS patients. However, the abovementioned findings need to be further confirmed in the next researches.
Continuous trigonometric collocation polynomial approximations with geometric and superconvergence analysis for efficiently solving semi-linear highly oscillatory hyperbolic systems
Authors: Liu Changying , Wu Xinyuan 
Published: February 2021

AbstractIn this paper, based on the continuous collocation polynomial approximations, we derive and analyse a class of trigonometric collocation integrators for solving the highly oscillatory hyperbolic system. The symmetry, convergence and energy conservation of the continuous collocation polynomial approximations are rigorously analysed in details. Moreover, we also proved that the continuous collocation polynomial approximations could achieve at superconvergence by choosing suitable collocation points. Numerical experiments verify our theoretical analysis results, and demonstrate the remarkable superiority in comparison with the traditional temporal integration methods in the literature.
A phase Ib, open-label, dose-escalation trial of the anti-CD37 monoclonal antibody, BI 836826, in combination with gemcitabine and oxaliplatin in patients with relapsed/refractory diffuse large B-cell lymphoma
Authors: Balzarotti Monica , Magagnoli Massimo , Canales Miguel Ángel , Corradini Paolo , Grande Carlos , Sancho Juan-Manuel , Zaja Francesco , Quinson Anne-Marie , Belsack Valérie , Maier Daniela , Carlo-Stella Carmelo 
Published: February 2021

SummaryBackground BI 836826 is a chimeric mouse–human monoclonal antibody directed against human CD37, a transmembrane protein expressed on mature B lymphocytes. This open-label, phase I dose-escalation trial (NCT02624492) was conducted to determine the maximum tolerated dose (MTD), safety/tolerability, and preliminary efficacy of BI 836826 in combination with gemcitabine and oxaliplatin in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Methods Eligible patients received intravenous infusions of BI 836826 on day 8 and gemcitabine 1000 mg/m2 plus oxaliplatin 100 mg/m2 on day 1, for up to six 14-day treatment cycles. Dose escalation followed the standard 3 + 3 design. Results Of 21 treated patients, 17 had relapsed/refractory DLBCL and four had follicular lymphoma transformed to DLBCL. BI 836826 dosing started at 25 mg and proceeded through 50 mg and 100 mg. Two dose-limiting toxicities (DLTs) occurred during cycle 1, both grade 4 thrombocytopenia lasting > 7 days, affecting 1/6 evaluable patients (17%) in both the 50 mg and 100 mg cohorts. Due to early termination of the study, the MTD was not determined. The most common adverse events related to BI 836826 treatment were neutropenia (52%), thrombocytopenia (48%), and anemia (48%). Eight patients (38%) experienced BI 836826-related infusion-related reactions (two grade 3). Overall objective response rate was 38%, including two patients (10%) with complete remission and six patients (29%) with partial remission. Conclusions BI 836826 in combination with GemOx was generally well tolerated but did not exceed the MTD at doses up to 100 mg given every 14 days.