bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of water hardness on zinc toxicity in Daphnia magna
Authors: Paylar Berkay , Asnake Solomon , Sjöberg Viktor , Ragnvaldsson Daniel , Jass Jana , Olsson Per‐Erik 
Published: March 2022

AbstractZinc is an essential trace metal required for the maintenance of multiple physiological functions. Due to this, organisms can experience both zinc deficiency and toxicity. Hardness is recognized as one of the main modifying physiochemical factors regulating zinc bioavailability. Therefore, the present study analyzed the effect of hardness on zinc toxicity using Daphnia magna. Endpoint parameters were acute‐toxicity, development, reproduction, and expression data for genes involved in metal regulation and oxidative stress. In addition, the temporal expression profiles of genes during the initiation of reproduction and molting were investigated. Water hardness influenced the survival in response to exposures to zinc. A zinc concentration of 50 μg/l in soft water (50 mg CaCO3/L) caused 73% mortality after 96 h exposure, whereas the same zinc concentration in the hardest water did not cause any significant mortality. Moreover, increasing water hardness from 100 to 200 mg CaCO3/L resulted in a reduced number of offspring. Fecundity was higher at first brood for groups exposed to higher Zn concentrations. The survival data were used to assess the precision of the bioavailability models (Bio‐met) and the geochemical model (Visual MINTEQ). As the Bio‐met risk predictions overestimated the Zn toxicity, a competition‐based model to describe the effects of hardness on zinc toxicity is proposed. This approach can be used to minimize differences in setting environmental quality standards. Moreover, gene expression data showed that using the toxicogenomic approach was more sensitive than the physiological endpoints. Therefore, data presented in the study can be used to improve risk assessment for zinc toxicity.
Label‐free single‐shot imaging with on‐axis phase‐shifting holographic reflectance quantitative phase microscopy
Authors: Liu Hanzi , Wu Xiaoyan , Liu Guodong , Ren Hongliang , R. V. Vinu , Chen Ziyang , Pu Jixiong 
Published: March 2022

AbstractQuantitative phase microscopy (QPM) has been emerged as an indispensable diagnostic and characterization tool in biomedical imaging with its characteristic nature of label‐free, noninvasive, and real time imaging modality. The integration of holography to the conventional microscopy opens new advancements in QPM featuring high‐resolution and quantitative three‐dimensional image reconstruction. However, the holography schemes suffer in space‐bandwidth and time‐bandwidth issues in the off‐axis and phase‐shifting configuration, respectively. Here, we introduce an on‐axis phase‐shifting holography based QPM system with single‐shot imaging capability. The technique utilizes the Fizeau interferometry scheme in combination with polarization phase‐shifting and space‐division multiplexing to achieve the single‐shot recording of the multiple phase‐shifted holograms. Moreover, the high‐speed imaging capability with instantaneous recording of spatially phase shifted holograms offers the flexible utilization of the approach in dynamic quantitative phase imaging with robust phase stability. We experimentally demonstrated the validity of the approach by quantitative phase imaging and depth‐resolved imaging of paramecium cells. Furthermore, the technique is applied to the phase imaging and quantitative parameter estimation of red blood cells. This integration of a Fizeau‐based phase‐shifting scheme to the optical microscopy enables a simple and robust tool for the investigations of engineered and biological specimen with real‐time quantitative analysis.
Necroptotic TNFα-Syndecan 4-TNFα Vicious Cycle as a Therapeutic Target for Preventing Temporomandibular Joint Osteoarthritis
Authors: He Feng , Ma Yuanjun , Li Shi , Ren Haozhe , Liu Qian , Chen Xiaohua , Miao Hui , Ye Tao , Lu Qian , Yang Zuge , Li Tianle , Tong Xin , Yang Hongxu , Zhang Mian , Wang Helin , Wang Yazhou , Yu Shibin 
Published: March 2022

ABSTRACT
Temporomandibular joint osteoarthritis (TMJOA) is a chronic degenerative disease for which the underlying mechanism still remains unclear. Compared with apoptosis and autophagy, necroptosis causes greater harm to tissue homeostasis by releasing damage-associated molecular patterns (DAMPs). However, the role of necroptosis and downstream key DAMPs in TMJOA is unknown. Here, rodent models of TMJOA were established by the unilateral anterior crossbite (UAC). Transmission electron microscopy (TEM) and immunohistochemistry of receptor interacting protein kinase 3 (RIPK3)/phosphorylation of mixed lineage kinase domain-like protein (pMLKL) were conducted to evaluate the occurrence of necroptosis in vivo. The therapeutic effects of blocking necroptosis were achieved by intra-articularly injecting RIPK3 or MLKL inhibitors and using RIPK3 or MLKL knockout mice. In vitro necroptosis of condylar chondrocyte was induced by combination of tumor necrosis factor alpha (TNFα), second mitochondria-derived activator of caspases (SMAC) mimetics and carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]- fluoromethylketone (z-VAD-fmk). The possible DAMPs released by necroptotic chondrocytes were screened by quantitative proteomics and blocked by specific antibody. Translucent cytosol, swollen organelles, and ruptured cell membranes, features of necroptosis, were frequently manifested in chondrocytes at the early stage of condylar cartilage degeneration in TMJOA, which was accompanied by upregulation of RIPK3/pMLKL. Inhibiting or knocking out RIPK3/MLKL significantly prevented cartilage degeneration. DAMPs released by necroptotic condylar chondrocytes, such as syndecan 4 (SDC4) and heat shock protein 90 (HSP90), were verified. Furthermore, blocking the function of SDC4 significantly attenuated the expression of TNFα in cartilage and synovium, and accordingly increased cartilage thickness and reduced synovial inflammation. Thus, the necroptotic vicious cycle of TNFα-SDC4-TNFα contributes to cartilage degeneration and synovitis, and can serve as a potential therapeutic target for treating TMJOA. © 2022 American Society for Bone and Mineral Research (ASBMR).
A real space picture of the role of steric effects inSN2reactions
Authors: Gallegos Miguel , Costales Aurora , Martín Pendás Ángel 
Published: March 2022

AbstractWithin substitution reactions, the Bimolecular Nucleophilic Substitution (SN2) reaction mechanism is one of the most frequently found and studied ones. Among other factors, the easiness of the SN2 pathway is classically considered to be determined by steric hindrance. However, the diffuse nature of the latter inevitably darkens these and other arguments holding the pillars of chemical intuition. In this work, we employ the steric energy (EST) descriptor, formulated within the Interacting Quantum Atoms approach, to offer insights regarding this problem. The steric demands of the substrate, nucleophile and leaving group were studied using the gas‐phase SN2 reaction with different organic skeletons (CH3, CH3CH2, (CH3)2CH, (CH3)3C, (CH3)3CCH2) and halogens (F, Cl, and Br) as test‐bed systems. Our results show that, according to EST, the SH experienced along these simple reactions fits, in the general case, the trends predicted by a meticulous and rigorous application of chemical intuition. However, steric clash alone should not be considered as the only argument used to explain the easiness of the SN2 reaction over different electrophiles.
Analysis of HIV‐1 integrase genotypes and polymorphisms among integrase inhibitors‐based antiretroviral treatment naïve patients in South Sudan
Authors: Giovanetti Marta , Farcomeni Stefania , Sernicola Leonardo , Virtuoso Sara , Fontanelli Sulekova Lucia , Maggiorella Maria T , Buttò Stefano , Taliani Gloria , Ciccozzi Massimo , Borsetti Alessandra 
Published: March 2022

AbstractHIV‐1 genetic diversity and drug resistance mutations remain public health challenges especially in regions where treatment is limited. The aim of this study was to characterize the HIV‐1 integrase (IN) subtype and the possible occurrence of drug‐resistance mutations or polymorphisms in resource‐poor settings in South Sudan. Dried blood spots from integrase inhibitor treatment (Integrase strand transfer inhibitor [INSTI]) naïve HIV‐1 infected patients were subjected to DNA amplification and direct sequencing of integrase genes. The sequences were interpreted for drug resistance according to the Stanford algorithm and the International AIDS Society‐USA guidelines. Phylogenetic analysis revealed that HIV‐1 subtype D, C, G, A1, and recombinant forms accounted for 40%, 10%, 13.3%, 23.4%, and 13.3%, respectively. Furthermore, inter‐subtype recombinants were interspersed within viral strains sampled in other African countries, highlighting complex transmission dynamics within a mobile host population. A total of 78 of 288 (27%) amino acid IN positions presented at least one polymorphism each. Major INSTI resistance mutations were absent, however, polymorphic accessory mutations at positions M50ILR (26.6%) and L74I (3.3%) were detected. Despite the limited size of the study population, our findings underscore the need for monitoring minor and natural polymorphisms that may influence the outcome of treatment regimens.
The impact of anti‐COVID‐19 nonpharmaceutical interventions on hand, foot, and mouth disease—A spatiotemporal perspective in Xi'an, northwestern China
Authors: Shen Li , Sun Minghao , Song Shuxuan , Hu Qingwu , Wang Nuoya , Ou Guangyu , Guo Zhaohui , Du Jing , Shao Zhongjun , Bai Yao , Liu Kun 
Published: March 2022

AbstractGrowing evidence has shown that anti‐COVID‐19 nonpharmaceutical interventions (NPIs) can support prevention and control of various infectious diseases, including intestinal diseases. However, most studies focused on the short‐term mitigating impact and neglected the dynamic impact over time. This study is aimed to investigate the dynamic impact of anti‐COVID‐19 NPIs on hand, foot, and mouth disease (HFMD) over time in Xi'an City, northwestern China. Based on the surveillance data of HFMD, meteorological and web search data, Bayesian Structural Time Series model and interrupted time series analysis were performed to quantitatively measure the impact of NPIs in sequent phases with different intensities and to predict the counterfactual number of HFMD cases. From 2013 to 2021, a total number of 172,898 HFMD cases were reported in Xi'an. In 2020, there appeared a significant decrease in HFMD incidence (−94.52%, 95% CI: −97.54% to −81.95%) in the first half of the year and the peak period shifted from June to October by a small margin of 6.74% compared to the previous years of 2013 to 2019. In 2021, the seasonality of HFMD incidence gradually returned to the bimodal temporal variation pattern with a significant average decline of 61.09%. In particular, the impact of NPIs on HFMD was more evident among young children (0–3 years), and the HFMD incidence reported in industrial areas had an unexpected increase of 51.71% in 2020 autumn and winter. Results suggested that both direct and indirect NPIs should be implemented as effective public health measures to reduce infectious disease and improve surveillance strategies, and HFMD incidence in Xi'an experienced a significant rebound to the previous seasonality after a prominent decline influenced by the anti‐COVID‐19 NPIs.
Baseline sensitivity of Rhizoctonia solani to four DMI fungicides
Authors: Gao Shigang , Xu Lihui , Zeng Rong , Gao Ping , Song Zhiwei , Dai Fuming 
Published: March 2022

AbstractA set of 78 Rhizoctonia solani isolates from Shanghai, China, were examined for their sensitivity in vitro to four demethylase inhibitor (DMI) fungicides, epoxiconazole, difenoconazole, hexaconazole, and tebuconazole, by the mycelial growth rate method. The isolates were very sensitive to the four DMI fungicides. The ranges and means of the EC50 values were 0.004–0.045 and 0.014 ± 0.007 μg ml−1 for epoxiconazole, 0–0.103 and 0.010 ± 0.016 μg ml−1 for difenoconazole, 0.001–0.078 and 0.011 ± 0.013 μg ml−1 for hexaconazole, and 0.001–0.210 and 0.034 ± 0.035 μg ml−1 for tebuconazole, respectively. The frequency distribution of the EC50 values showed a normal curve for epoxiconazole and an approximately unimodal curve for difenoconazole, hexaconazole, and tebuconazole. There was no correlation between the sensitivities of the R. solani population to any two of the four fungicides (r < 0.3). In field trials, in 2015 and 2016, the control efficacies of hexaconzole, epoxiconazole, and tebuconazole were >90.0% at 75 g.a.i. ha−1, 80.0%–90.0% at 75 g.a.i. ha−1 and 80.0%–90.0% at 97 g.a.i. ha−1, respectively; these values are significantly higher (p < 0.05) than those obtained in this study for difenoconazole (65.0%–70.0% at 80 g.a.i. ha−1) and jinggangmycin (68.0%–71.0% at 150 g.a.i. ha−1). These results show that sensitivity data can be used to monitor and detect any variations in the sensitivity of the R. solani population to these four DMI fungicides, and demonstrate that epoxiconazole, hexaconazole, and tebuconazole are likely to be good alternatives to jinggangmycin for controlling rice sheath blight.
Computational analysis of Lisfranc surgical repairs
Authors: Perez Michael T. , Owen John R. , Adelaar Robert S. , Wayne Jennifer S. 
Published: March 2022

AbstractLigamentous Lisfranc injuries cause debilitating pain and loss of function. Even small diastasis of this normally rigid joint after injury requires surgical treatment, but outcomes remain poor. Existing literature has compared the different surgical procedures using cadaveric models, but no approach has been recommended over others. This study uses a computational biomechanical approach consistent with a cadaveric study to evaluate the different procedures' ability to stabilize the Lisfranc joint without inducing secondary consequences. A validated rigid body model for the cadaver foot with a Lisfranc injury was extended to compare the stability of four different surgical repairs—three open reduction and internal fixation procedures with different hardware (cannulated screws, endobuttons, and screws with a dorsal plate) and primary arthrodesis with screws. Forces calculated from the rigid body model for 50% partial weight bearing provided boundary conditions for a finite element model of the surgical repairs. Comparing the different surgical procedures, the open reduction and internal fixation with screws and primary arthrodesis with screws showed the most stable postoperative Lisfranc joint. However, the use of cannulated screws for fixation showed regions of high stress that may be susceptible to breakage and also resulted in higher contact forces in joints adjacent to the surgery site. Endobuttons and dorsal plates did not restore sufficient stability. Since all procedures showed different points of concern that could impact outcomes, additional surgical approaches could be needed in the future. This study offers a standard protocol for benchmarking the new procedures against those currently used.
Modified low ratio ketogenic therapy in the treatment of adults with super‐refractory status epilepticus
Authors: Kaul Neha , Nation Judy , Laing Joshua , Nicolo John‐Paul , Deane Adam M. , Udy Andrew A. , Kwan Patrick , O'Brien Terence J. 
Published: March 2022

AbstractBackgroundInduction of ketosis by manipulation of nutrition intake has been proposed as an adjunctive treatment for super‐refractory status epilepticus (SRSE). However, the classical 4:1 ketogenic ratio may not meet the nutrition needs, specifically protein for critically ill adults. The aim of this study was to analyze the outcomes of adults with SRSE who received a lower ketogenic ratio of 2:1 grams of fat to non‐fat grams, including 20%–30% of energy from medium chain triglycerides.MethodsWe reviewed patients aged ≥18 years with SRSE treated with ketogenic therapy between July 2015 and December 2020 at two quaternary teaching hospitals in Melbourne, Australia. Data collected from medical records included patient demographics, nutrition prescription, clinical outcomes, and ketogenic therapy‐related complications. The primary outcome of the study was to assess tolerability of ketogenic therapy.ResultsTwelve patients (female = 7) were treated with ketogenic therapy for SRSE. Patients received between 4 and 8 antiseizure medications and 1–5 anesthetic agents prior to commencement of ketogenic therapy. Blood beta‐hydroxybutyrate concentrations were variable (median = 0.5 mmol/L, range: 0.0–6.1 mmol/L).SRSE resolved in 10 cases (83%) after a median of 9 days (range: 2–21 days) following commencement of ketogenic therapy. Ketogenic therapy–associated complications were reported in five patients, leading to cessation in two patients.ConclusionDespite the challenge in maintaining ketosis during critical illness, low ratio 2:1 ketogenic therapy incorporating medium chain triglycerides is tolerable for adults with SRSE. Further studies are required to determine the optimal timing, nutrition prescription and duration of ketogenic therapy for SRSE treatment.
Efficacy and safety of metaraminol in critically ill patients with shock: a systematic review
Authors: Sardaneh Arwa Abu , Narayan Sujita , Penm Jonathan , Oliver Matthew , Gattas David , McLachlan Andrew J. , Patanwala Asad E. 
Published: March 2022

AbstractAimTo assess the efficacy and safety of metaraminol infusions in comparison to other vasopressors in critically ill patients with shock with regard to hospital mortality, effect on haemodynamics (mean arterial pressure or systolic blood pressure), duration of vasopressor use, and adverse events.Data sourcesA systematic review was conducted in eight electronic databases and nine trial registers from inception to 17 March 2021.Study selectionStudies included randomised or non‐randomised controlled trials, and retrospective or prospective observational studies of critically ill adult patients admitted to the intensive care unit or emergency department with shock of any aetiology and who received metaraminol via continuous infusion compared to patients who received other vasopressors.ResultsOut of 1387 eligible articles, three observational studies and one controlled trial were included involving a total of 54 patients. Study patients had different types of shock including septic (n = 28), cardiogenic (n = 21), hypovolemic (n = 3) and neurogenic shock (n = 2). All studies compared metaraminol to noradrenaline and were of poor quality and high risk of bias. There was no difference in hospital mortality or effect on mean arterial pressure or systolic blood pressure between metaraminol and noradrenaline in any of the studies. None of the studies reported the duration of vasopressor use or adverse drug events such as extravasation or tissue injury.ConclusionThere is limited and low‐quality efficacy and safety data to support the use of metaraminol over other vasopressors in critically ill patients with shock. Future clinical trials are needed before this agent is routinely used in this patient population.
When is the evidence conclusive? Analysis of systematic reviews for which Cochrane declared that conclusions will not change with further studies
Authors: Babić Andrija , Poklepović Peričić Tina , Pieper Dawid , Puljak Livia 
Published: March 2022

AbstractSome Cochrane reviews were declared stable or closed, that is, not in need of updating. For some of them, it has been declared that conclusions will not (or it is unlikely they will) change with further studies. We explored whether there is a discernable decision‐making pattern for decisions about the conclusiveness and stabilization of these reviews. We analyzed Cochrane reviews published until April 2020 labeled as stable or closed. We extracted the rationale leading to the decision declaring that the conclusion is not expected to change with further studies. Furthermore, we assessed whether the reviews used GRADE analysis. We extracted data from summary of findings (SoF) tables on the direction of effect, statistical significance, and I2 values for the first and primary outcomes in SoFs, conclusions in the abstract and review, and implications for practice and future research. We included 40 stable/closed Cochrane reviews. Rationales for their stabilization did not enable any insight into the Cochrane's decision‐making algorithm for considering the evidence as conclusive. Among 191 outcomes presented in the SoFs, 70% were rated with either low or very low certainty evidence. None of the reviews mentioned in the text that the review should be stabilized or closed, or that there is sufficient evidence on the subject. Reasons for stabilizing/closing Cochrane reviews were unclear, and we could not discern any pattern of “conclusive review” traits. Definition of systematic review conclusiveness is still lacking, which may contribute to research waste.
Surgical resection for adrenocortical carcinoma: Current trends affecting survival
Authors: Shah Monali , NeMoyer Rachel E. , Kashyap Richi , Lin Yong , Sarmiento Juan , Kooby David A. , Maithel Shishir K. , Gillespie Theresa W. , Laird Amanda M. , Shah Mihir M. 
Published: March 2022

AbstractIntroductionAdrenocortical carcinoma (ACC) is associated with a poor prognosis. We reviewed the National Cancer Database (NCDB) to analyze the prognostic factors in surgically resected ACC patients and the association of surgical approaches with overall survival (OS).MethodsA retrospective NCDB (2004–2014) review of patients undergoing curative‐intent surgical resection for ACC was performed. Effects of patient demographics, tumor characteristics, histopathology, and perioperative course on OS were analyzed. Log‐rank statistics were used to associate clinical variables with OS. The multivariable Cox proportional hazard model included only statistically significant variables.ResultsA total of 1599 patients with ACC were included. A majority of patients were female (60.73%) and presented with a Charlson–Deyo score of zero (75.42%). A majority of the ACC cases were Grade 3 (45.69%), and almost a third (30.64%) underwent margin‐positive resections. Univariate analysis demonstrated a decrease in OS associated with increasing age and comorbidities. A negative resection margin and lack of lymphovascular invasion predicted better OS. Multivariable analysis showed that age, grade, surgical resection margins, and hospital length of stay were associated with OS.ConclusionsAdvanced age, grade, presence of lymphovascular invasion, and positive surgical margins predicted a worse overall survival for adrenocortical cancer in our analysis. Resection with negative margins improves outcomes.