bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD15+ tumor infiltrating granulocytic cells can predict recurrence and their depletion is accompanied by good responses to S‐1 with oral cancer
Authors: Seki‐Soda Mai , Sano Takaaki , Ogawa Masaru , Yokoo Satoshi , Oyama Tetsunari 
Published: April 2021

AbstractBackgroundIt has been reported in oral squamous cell carcinoma (OSCC) that myeloid‐derived suppressor cells infiltrate tumor tissues. This study examined whether S‐1 chemotherapy changes immune cell populations in the tumor microenvironment.MethodsWe examined 71 patients with of OSCC, including 51 patients who received preoperative S‐1 chemotherapy. Immunohistochemistry for PD‐L1, CD8, forkhead box protein 3 (FOXP3), and CD15 was performed using biopsy and resected specimens.ResultsThe numbers of CD8+, FOXP3+, and CD15+ cells in resected specimens were significantly decreased by S‐1 chemotherapy. The reduction of the proportion of CD15+ cells significantly differed between responders and nonresponders. Most responders were distributed into the group with low PD‐L1 expression and a low density of CD8+ cells before chemotherapy. Furthermore, many patients with recurrence exhibited a high density of CD15+ cells in biopsy specimens.ConclusionPreoperative S‐1 chemotherapy can potentially improve prognosis by reducing CD15+ cells in the tumor microenvironment.
High‐risk early‐stage oral tongue squamous cell carcinoma, when free margins are not enough: Critical review
Authors: Galli Andrea , Bondi Stefano , Canevari Carla , Tulli Michele , Giordano Leone , Di Santo Davide , Gianolli Luigi , Bussi Mario 
Published: April 2021

AbstractOral tongue squamous cell carcinoma (OTSCC) is a quite peculiar disease from an anatomical and biological standpoint. An increasing amount of literature highlights the existence of a small subset of T1‐T2N0 OTSCC, properly resected on a margin‐dependent basis, which conversely proved higher than expected rates of loco‐regional/distant failure and disease‐specific mortality. These specific high‐risk tumors might not have a margin‐dependent disease and could possibly benefit from a more aggressive upfront loco‐regional treatment, especially addressing the so‐called T‐N tract. Widespread adoption of a histopathological risk model would allow early recognition of these high‐risk diseases and, consequently, intensification of the traditional treatment strategies in that specific niche. We reviewed the available knowledge trying to shed light on the potential determinants of the dismal prognosis of these high‐risk OTSCC, with special reference to the role of overlooked T‐N tract involvement and possible alternatives in terms of elective neck management and risk stratification.
Impact of institutional constraints on participatory irrigation management: The regulating role of moral obligation*
Authors: Yang Liu , Ren Yang , Tang Zhiwei , Zhu Yuchun 
Published: April 2021

AbstractParticipatory irrigation management is key to realizing the virtuous circle in which irrigation facilities are used and managed in rural China. Therefore, it is essential to explore the key factors influencing participatory irrigation management. This paper innovatively analyses the impact of external institutional constraints and internal moral obligation of farmers on participatory irrigation management by using a structural equation model (SEM) and drawing on survey data from 1543 householders in the Yellow River basin. The results indicate that: (i) generally, both institutional constraints and moral obligation have significant positive impacts on collective action in participatory irrigation management; (ii) moral obligation plays an active regulating role in the process of institutional constraints affecting collective action; (iii) collective action contributes positively to the performance of participatory irrigation management. This paper shows that institutional constraints and moral obligation need to be taken into account in participatory irrigation management, and these considerations can offer some insights into governments in managing irrigation systems.
Detection of truncated isoforms of human neuroserpin lacking the reactive center loop: Implications in noninhibitory role
Authors: Fatima Sana , Ansari Shoyab , Bano Shadabi , Ahamad Shahzaib , Ishqi Hassan Mubarak , Tabish Mohammad , Gupta Dinesh , Rehman Sayeed Ur , Jairajpuri Mohamad Aman 
Published: April 2021

AbstractNeuroserpin is a serine protease inhibitor expressed mainly in the brain and at low levels in other tissues like the kidney, testis, heart, and spinal cord. It is involved in the inhibition of tissue plasminogen activator (tPA), plasmin, and to a lesser extent, urokinase‐type plasminogen (uPA). Neuroserpin has also been shown to plays noninhibitory roles in the regulation of N‐cadherin‐mediated cell adhesion. It is involved in neuroprotection from seizure and stroke through tPA‐mediated inhibition and also through its other protease targets. Mutations in critical domains of neuroserpin lead to its polymerization and neuronal death. In this study, a novel truncated isoform of human neuroserpin was identified in the brain and liver, which was confirmed by reverse transcriptase‐PCR and DNA sequencing using exon‐specific primers. Structural characterization of novel isoform using MD simulations studies indicated that it lacks the reactive center loop (RCL) but largely maintains its secondary structure fold. The novel truncated variant was cloned, expressed, and purified. A comparative intrinsic fluorescence and 4,4′‐bis‐1‐anilino naphthalene 8‐sulfonate studies revealed a decrease in fluorescence emission intensity and a more exposed hydrophobic surface as compared to the reported isoform. However, the novel isoform has lost its ability for tPA inhibition and complex formation. The absence of RCL indicates a noninhibitory role for the truncated isoform, prompting a detailed search and identification of two smaller isoforms in the human brain. With indications of the noninhibitory role of neuroserpin, identifying novel isoforms that appear to be without the tPA recognition domain is significant.
Biological compatibility, thermal and in vitro simulated degradation for poly(p‐dioxanone)/poly(lactide‐co‐glycolide)/poly(ethylene succinate‐co‐glycolide)
Authors: Zhong Gang , Liu Yihao , Liu Canpei , Li Xu , Lin Jingwei , Lanzon Alain Luigi , Zhang Huagui , Chen Mingfeng 
Published: April 2021

AbstractBio‐absorbable polymers are widely desired to be applied and used as biomaterials for surgery hemostatic and medical tissue engineering devices. Ring‐opening copolymerization reaction was applied to synthesize poly(ethylene succinate‐co‐glycolide) (PES‐b‐PGA). Stannous octoate was used as a catalyst whereas poly(ethylene succinate) was used as a macro‐initiator to react with glycolide. PES‐b‐PGA was then used as a compatibilizer to prepare the blend biomaterial of PPDO/PLGA/PES‐b‐PGA by melt blending poly(p‐dioxanone) (PPDO) with poly(lactide‐co‐glycolide) (PLGA). This would enhance the interactions of the inter‐molecular chains and intra‐molecular segments thus improving the compatibility. To obtain the biomaterial of PPDO/PLGA/PES‐b‐PGA with a regulated and controlled degradation and/or hydrolysis period, various ratios of PPDO, PLGA, and PES‐b‐PGA was blended. Behaviors of the thermal and in vitro simulated degradation, biological compatibility, cytotoxicity and subcutaneous implantation of PPDO/PLGA/PES‐b‐PGA were investigated. The results show that the in vitro hydrolytic degradation cycle is consistent with the wound healing time and that the biomaterial has slight cytotoxicity and it will do good to the cell proliferation, with 1 grade of cytotoxicity and the relative growth rate being the range from 92.5% to 96.2%. The implantation of the biomaterial into the rabbits' ears will not adversely affect the wound healing and the tissues surrounding the implanted sites. Therefore, the biomaterial has good biocompatibility and potential applications in medical tissue engineering devices.
A Population Pharmacokinetic Meta‐Analysis of Veliparib, a PARP Inhibitor, Across Phase 1/2/3 Trials in Cancer Patients
Authors: Stodtmann Sven , Nuthalapati Silpa , Eckert Doerthe , Kasichayanula Sreeneeranj , Joshi Rujuta , Bach Bruce A. , Mensing Sven , Menon Rajeev , Xiong Hao 
Published: April 2021

AbstractVeliparib (ABT‐888) is a poly(ADP‐ribose) polymerase inhibitor in development for the treatment of high‐grade ovarian cancer or BRCA‐mutated breast cancer in combination with carboplatin and paclitaxel. The population pharmacokinetics of veliparib were characterized using combined data from 1470 adult subjects with ovarian cancer, breast cancer, or other solid tumors enrolled in 6 phase 1 studies, 1 phase 2 study, and 2 phase 3 studies of veliparib oral doses of 10 to 400 mg twice daily as monotherapy or in combination with chemotherapy. A 1‐compartment model with linear clearance and first‐order absorption best characterized veliparib pharmacokinetics. The predicted apparent oral clearance (CL/F) and volume of distribution (Vc/F) were 479 L/day and 152 L, respectively. The significant covariates in the final model included albumin, creatinine clearance, strong inhibitors of cytochrome P450 (CYP) 2D6, and sex on CL/F and albumin, body weight, and sex on Vc/F. Mild and moderate renal impairment increased veliparib median (95%CI) steady‐state AUC (AUCss) by 27.3% (23.7%‐30.9%) and 65.4% (56.0%‐75.5%), respectively, compared with normal renal function. Male subjects had 16.5% (7.53%‐23.9%) lower AUCss compared with female subjects and coadministration with strong CYP2D6 inhibitors increased AUCss by 13.0% (6.11%‐20.8%). Race, age, region, cancer type, or enzyme (CYP3A4, CYP2C19) or transporter (P‐glycoprotein, multidrug and toxin extrusion protein 1/2, organic cation transporter 2) inhibiting/inducing comedications were not found to significantly impact veliparib pharmacokinetics. Other than baseline creatinine clearance and hence renal impairment effect on veliparib clearance, no other covariates had a clinically meaningful effect on veliparib exposure warranting dose adjustment.
Between responsibility and desire: Accounts of reproductive decisions from those at risk for or affected by late‐onset neurological diseases
Authors: Mendes Álvaro , Sequeiros Jorge , Clarke Angus J. 
Published: April 2021

AbstractThis paper explores ways in which genetic risk foregrounds forms of responsibility while dealing with reproduction. We analyzed individual and family semi‐structured interviews (n = 35) with people at‐risk for or affected by transthyretin‐related familial amyloid polyneuropathy (TTR‐FAP) and Machado‐Joseph disease (MJD), which are late‐onset neurological diseases. Although generally considered as rare diseases, some areas in Portugal present the world's highest frequency for MJD and TTR‐FAP. Thematic analysis of the data revealed that participants drew on various – sometimes ambivalent and competing – understandings of their genetic risk and their wish to have children. Some participants perceived the avoidance of genetic risk to be responsible behavior, while, for others, responsibility entailed accepting risks because they prioritized values such as parenthood, family relationships and the value of life, above any question of genetic disease. Some participants shared accounts that were fraught with ambivalence, repentance and guilt, especially when children were born before participants knew of their own or their partner's risk. Participants’ accounts also showed they make continued efforts to see themselves as responsible persons and to appear responsible in the eyes of others. We discuss findings in the context of participants’ negotiation between genetic risk and their sense of responsibility toward themselves and others; we conclude that “genetic responsibility” is present not only in accounts of those who chose not to have children but also in those who make an informed decision to have at‐risk children.
Interaction analysis of gene variants related to one‐carbon metabolism with chronic hepatitis B infection in Chinese patients
Authors: Sun Yao‐Hui , Gao Jie , Liu Xu‐Dong , Tang Hong‐Wei , Cao Sheng‐Li , Zhang Jia‐Kai , Wen Pei‐Hao , Wang Zhi‐Hui , Li Jie , Guo Wen‐Zhi , Zhang Shui‐Jun 
Published: April 2021

AbstractBackgroundThe risk of chronic hepatitis B (CHB) infection is influenced by aberrant DNA methylation and altered nucleotide synthesis and repair, possibly caused by polymorphic variants in one‐carbon metabolism genes. In the present study, we investigated the relationship between polymorphisms belonging to the one‐carbon metabolic pathway and CHB infection.MethodsA case–control study using 230 CHB patients and 234 unrelated healthy controls was carried out to assess the genetic association of 24 single nucleotide polymorphisins (SNPs) determined by mass spectrometry.ResultsThree SNPs, comprising rs10717122 and rs2229717 in serine hydroxymethyltransferase1/2 (SHMT2) and rs585800 in betaine‐homocysteine S‐methyltransferase (BHMT), were associated with the risk of CHB. Patients with DEL allele, DEL.DEL and DEL.T genotypes of rs10717122 had a 1.40‐, 2.00‐ and 1.83‐fold increased risk for CHB, respectively. Cases inheriting TA genotype of rs585800 had a 2.19‐fold risk for CHB infection. The T allele of rs2229717 was less represented in the CHB cases (odds ratio = 0.66, 95% confidence interval = 0.48–0.92). The T allele of rs2229717 was less in patients with a low hepatitis B virus‐DNA level compared to the control group (odds ratio = 0.49, 95% confidence interval = 0.25–0.97) and TT genotype of rs2229717 had a significant correlation with hepatitis B surface antigen level (p = 0.0195). Further gene–gene interaction analysis showed that subjects carrying the rs10717122 DEL.DEL/DEL.T and rs585800 TT/TA genotypes had a 2.74‐fold increased risk of CHB.ConclusionsThe results of the present study suggest that rs10717122, rs585800 and rs2229717 and gene–gene interactions of rs10717122 and rs585800 affect the outcome of CHB infection, at the same time as indicating their usefulness as a predictive and diagnostic biomarker of CHB infection.
Quantitative 3D Ultrashort Echo Time Magnetization Transfer Imaging for Evaluation of Knee Cartilage Degeneration In Vivo
Authors: Xue Yan‐Ping , Ma Ya‐Jun , Wu Mei , Jerban Saeed , Wei Zhao , Chang Eric Y. , Du Jiang 
Published: April 2021

BackgroundRecent studies suggest that macromolecular fraction (MMF) derived from three‐dimensional ultrashort echo time magnetization transfer (UTE‐MT) imaging is insensitive to the magic angle effect. However, its clinical use in osteoarthritis (OA) remains to be investigated.PurposeTo investigate the feasibility of 3D UTE‐MT‐derived MMF in differentiating normal from degenerated cartilage.Study TypeProspective.SubjectsSixty‐two participants (54.8 ± 16.7 years, 30 females) with and without OA, plus two healthy volunteers (mean age 35.0 years) for reproducibility test.Field Strength/Sequence3 T/UTE‐MT sequence.AssessmentA 3D UTE‐MT sequence was employed to calculate MMF based on a two‐pool model. Kellgren–Lawrence (KL) grade and Whole‐Organ Magnetic Resonance Imaging Score (WORMS) were evaluated by three experienced musculoskeletal radiologists. KL grade was condensed into three groups: KL0, KL1–2, and KL3–4. WORMS was regrouped based on extent of lesion (extent group) and depth of lesion (depth group), respectively. The performance of MMF at evaluating the degeneration of cartilage was assessed via Spearman's correlation coefficient and the area under the curve (AUC) calculated according to the receiver‐operating characteristic curve.Statistical TestsAfter normality check, one‐way analysis of variance was used to evaluate the performance. Tukey–Kramer test was performed for post hoc testing.ResultsMMF showed significant negative correlations with KL grade (r = −0.53, P < 0.05) and WORMS (r = −0.49, P < 0.05). Significantly lower MMFs were found in subjects with greater KL grade (11.8 ± 0.8% for KL0; 10.9 ± 0.9% for KL1–2; 10.6 ± 1.1% for KL3–4; P < 0.05) and in cartilage with greater extent (12.1 ± 1.6% for normal cartilage; 10.9 ± 1.6% for regional lesions; 9.6 ± 1.7% for diffuse lesions; P < 0.05) and depth (12.1 ± 1.6% for normal cartilage; 10.6 ± 1.6% for partial‐thickness lesions; 8.8 ± 1.7% for full‐thickness lesions; P < 0.05) of lesions. AUC values of MMF for doubtful‐minimal OA (KL1–2) and mild cartilage degradation (WORMS1–2) were 0.8 and 0.7, respectively.Data ConclusionThis study highlights the clinical potential of MMF in the detection of early OA.Level of Evidence2Technical Efficacy Stage2
Structural optimization method of foldable active‐matrix organic light‐emitting diode panel based on mechanical theory
Authors: Wu Di , Liao Dunming , Shi Junke , Jia Yongzhen 
Published: April 2021

AbstractThe multineutral plane phenomenon of foldable panel can obviously reduce the strain of the active‐matrix organic light‐emitting diode (AMOLED) panel after being bent, but it also complicates the optimization of the panel structure. Considering the force balance at the axis of symmetry after the panel was folded, this paper established the basic theory of AMOLED panel structure optimization, which indicated the direction of structure optimization of the panel. Then, the theory was validated by numerical simulation. It can be used to guide the structural design of the foldable panel.
Predictors of early recurrence following neoadjuvant chemotherapy and surgical resection for localized pancreatic adenocarcinoma
Authors: Narayanan Sowmya , AlMasri Samer , Zenati Mazen , Nassour Ibrahim , Chopra Asmita , Rieser Caroline , Smith Katelyn , Oyefusi Vivianne , Daum Tracy , Bahary Nathan , Bartlett David , Lee Kenneth , Zureikat Amer , Paniccia Alessandro 
Published: April 2021

AbstractBackground and ObjectivesNeoadjuvant chemotherapy (NAT) for pancreatic adenocarcinoma (PDAC) is increasingly being utilized. However, a significant number of patients will experience early recurrence, possibly negating the benefit of surgery. We aimed to identify factors implicated in early disease recurrence.MethodsA retrospective review of pancreaticoduodenectomies performed between 2005 and 2017 at our institution for PDAC following NAT was performed. A 6‐month cut‐off was used to stratify patients into early/late recurrence groups. Multivariate analysis was performed to identify predictors of recurrence.ResultsOf 273 patients, 64 (23%) developed early recurrence or died within 90 days of surgery. The median time to recurrence was 4 months (95% confidence interval [CI]: 2.2–4.3) in the early group versus 16 months (95% CI: 13.7–19.9) in the late group. The former had higher baseline and post‐NAT Ca19‐9 levels than the latter (472 vs. 153 IU/ml, p = 0.001 and 71 vs. 39 IU/ml, p = 0.005, respectively). A higher positive lymph node ratio significantly increased the risk of early recurrence (hazard ratio [HR]: 15.9, p < 0.001) while adjuvant chemotherapy was protective (HR: 0.4, p < 0.001).ConclusionOur findings acknowledge the limitations of clinically measured factors used to ascertain response to NAT and underline the need for individualized molecular markers that take into consideration the specific tumor biology.
Modified Head and Neck Swallow Scale: Using EORTC‐QLQ‐H&N35 to Predict Overall Survival
Authors: von Allmen Douglas , Tang Alice , Takiar Vinita , Zender Chad , Romeo Stephen , Masch Jessica , Casper Keith , Patil Yash , Wilson Keith , Khosla Siddarth , Niu Liang , Altaye Mekibib , Tabangin Meredith , Howell Rebecca J. 
Published: April 2021

Objectives/HypothesisDysphagia is a treatment‐related complication of head and neck cancer (HNCA). We demonstrate the predictive value of a modified head and neck swallow scale (m‐HNSW) adapted from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire‐Head and Neck 35 (EORTC‐QLQ‐H&N35).Study DesignRetrospective Cohort Study.MethodsRetrospective, single‐center cohort study utilizing a prospectively collected database of HNCA patients in a high‐volume tertiary referral center. 736 HNCA patients more than 2 years from completion of treatment were identified. EORTC‐QLQ‐H&N35 data collected from at least one of three defined episodes of care were used. The m‐HNSW uses three questions to form a 9‐point dysphagia scale. A Cox proportional hazards model was used to determine the effect of the m‐HNSW while controlling for demographics, tumor staging, site, and treatment.ResultsUsing data from 3, 6, 12 months from treatment, we analyzed a subset that included 328 patients. Three months after the completion of therapy, the m‐HNSW score had a significant association with 1 (HR = 1.24, P = .0005) and 5 year survival (HR = 1.19, P = .0002) after accounting for body mass index. Six (HR = 1.14, P = .014) and 12 month (hazard ratio (HR) = 1.33, P < .0001) scores post completion of therapy predict 5‐year survival. An increase of the m‐HNSW score by 1 point was associated with an increase in death by 24%, and 19% at 1 and 5 years following therapy.ConclusionsThe m‐HNSW is a simple assessment of dysphagia using previously validated EORTC‐QLC‐H&N35 data that when taken at 3, 6, and 12 months after completion of therapy is predictive of overall survival.Level of Evidence4 Laryngoscope, 131:2478–2482, 2021
Manganese biogeochemistry in the Southern Ocean, from Tasmania to Antarctica
Authors: Latour Pauline , Wuttig Kathrin , van der Merwe Pier , Strzepek Robert F. , Gault‐Ringold Melanie , Townsend Ashley T. , Holmes Thomas M. , Corkill Matthew , Bowie Andrew R. 
Published: April 2021

AbstractManganese (Mn) is an abundant element in the Earth's crust. However, its concentrations in open ocean seawater are low, where external inputs are scarce. In this study, we report the dissolved Mn and particulate Mn distributions in the Southern Ocean, measured along the GEOTRACES—SR3 transect, from Tasmania (Australia) to Antarctica in the Southern Ocean, during the austral summer 2018. Both dissolved Mn and particulate Mn concentrations were generally low away from localized sources (< 0.3 nmol L−1 and < 0.1 nmol L−1, respectively) along the transect. Our observations of a lower labile particulate fraction than previously measured suggest the Southern Ocean has a unique particulate Mn composition. Low surface dissolved Mn concentrations were attributed to biological uptake and few external sources. Our results suggest biological control of the Mn cycle was higher above the Antarctic continental slope, compared to the rest of the section, and our particulate Mn : P ratios indicated the presence of iron‐stressed diatoms south of the Sub‐Antarctic Front. We suggest low dissolved Mn surface concentrations may (co‐)limit phytoplankton growth in this region. Localized higher dissolved Mn concentrations were observed due to external sources, such as sedimentary and hydrothermal inputs. The presence of an eddy at the same latitude as a hydrothermal plume induced an upwelling of hydrothermally enriched waters up to 1000 m; however, no dissolved Mn inputs to the surface waters were observed. We suggest previous dissolved Mn inputs to the surface layer may be obscured by biological uptake.
In Vivo Degradation Mechanisms of Aliphatic Polycarbonates and Functionalized Aliphatic Polycarbonates
Authors: Amsden Brian 
Published: April 2021

AbstractAliphatic polycarbonates (APCs) have been studied for decades but have not been as utilized as aliphatic polyesters in biomaterial applications such as drug delivery and tissue engineering. With the recognition that functionalized aliphatic polymers can be readily synthesized, increased attention is being paid to these materials. A frequently provided reason for utilizing these polymers is that they degrade to form diols and carbon dioxide. However, depending on the structure and molecular weight of the APC, degradation may not occur. In this review, the mechanisms by which APCs and functionalized APCs have been found to degrade in vivo are examined with the objective of providing guidance in the continued development of these polymers as biomaterials.