bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of lenvatinib monotreatment and lenvatinib-based combination therapy for patients with unresectable hepatocellular carcinoma: a retrospective, real-world study in China
Authors: Zhu Yun , Sun Penghui , Wang Kunyuan , Xiao Shuzhe , Cheng Yanling , Li Xiangzhao , Wang Biao , Li Jiancong , Yu Wenxuan , Cheng Yang 
Published: September 2021

Abstract
Background
Lenvatinib and lenvatinib-based combination treatments are widely used in patients with unresectable hepatocellular carcinoma (uHCC) in clinical practice, but their curative effect and safety need further study in the real world.

Methods
This was a retrospective study involving patients with uHCC receiving lenvatinib monotherapy and lenvatinib-based combination treatment between Nov, 2018 and Sep, 2020 in Nanfang Hospital. Efficacy was evaluated with objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), time to tumor progression (TTP), and overall survival (OS). Treatment-related adverse events (TRAEs) were recorded and graded. Efficacy and safety of monotherapy and combination therapy were compared. Stratified analysis was performed according to systemic line of treatment and medication regimen for combination therapy.

Results
For lenvatinib monotherapy (n = 39), OS and PFS were 80 weeks and 24.3 weeks, respectively. For combination treatment (n = 72), median OS and PFS were 99 weeks and 45.6 weeks, respectively. OS, PFS, and TTP for patients in the combination treatment cohort were significantly longer compared to those of patients in the monotreatment cohort (OS: P = 0.04, PFS: P = 0.003; TTP, P = 0.005). The incidence of TRAEs could be controlled both in the monotherapy cohort and the combination treatment cohort. In the monotherapy cohort, OS and PFS were significantly decreased in the second-line treatment group compared with the first-line treatment group, while no differences were observed in the combination cohort. The efficacy of triple therapy (lenvatinib plus PD-1 antibody plus TACE or HAIF) was similar to lenvatinib plus PD-1 antibody or lenvatinib plus TACE or HAIF.

Conclusions
Our real-world study showed that lenvatinib monotherapy and lenvatinib-based combination therapy were well tolerated, with encouraging efficacies in patients with uHCC. Lenvatinib-based combination therapy showed a better curative effect compared with lenvatinib single-agent therapy. In patients who have failed first-line TKI treatment, lenvatinib-based combination therapy may be a better choice than lenvatinib single-agent therapy. Lenvatinib-based triple therapy may not have an advantage over dual therapy.
Climate change, extreme events, and increased risk of salmonellosis: foodborne diseases active surveillance network (FoodNet), 2004-2014
Authors: Morgado Michele E. , Jiang Chengsheng , Zambrana Jordan , Upperman Crystal Romeo , Mitchell Clifford , Boyle Michelle , Sapkota Amy R. , Sapkota Amir 
Published: September 2021

Abstract
Background
Infections with nontyphoidal Salmonella cause an estimated 19,336 hospitalizations each year in the United States. Sources of infection can vary by state and include animal and plant-based foods, as well as environmental reservoirs. Several studies have recognized the importance of increased ambient temperature and precipitation in the spread and persistence of Salmonella in soil and food. However, the impact of extreme weather events on Salmonella infection rates among the most prevalent serovars, has not been fully evaluated across distinct U.S. regions.

Methods
To address this knowledge gap, we obtained Salmonella case data for S. Enteriditis, S. Typhimurium, S. Newport, and S. Javiana (2004-2014; n = 32,951) from the Foodborne Diseases Active Surveillance Network (FoodNet), and weather data from the National Climatic Data Center (1960-2014). Extreme heat and precipitation events for the study period (2004-2014) were identified using location and calendar day specific 95th percentile thresholds derived using a 30-year baseline (1960-1989). Negative binomial generalized estimating equations were used to evaluate the association between exposure to extreme events and salmonellosis rates.

Results
We observed that extreme heat exposure was associated with increased rates of infection with S. Newport in Maryland (Incidence Rate Ratio (IRR): 1.07, 95% Confidence Interval (CI): 1.01, 1.14), and Tennessee (IRR: 1.06, 95% CI: 1.04, 1.09), both FoodNet sites with high densities of animal feeding operations (e.g., broiler chickens and cattle). Extreme precipitation events were also associated with increased rates of S. Javiana infections, by 22% in Connecticut (IRR: 1.22, 95% CI: 1.10, 1.35) and by 5% in Georgia (IRR: 1.05, 95% CI: 1.01, 1.08), respectively. In addition, there was an 11% (IRR: 1.11, 95% CI: 1.04-1.18) increased rate of S. Newport infections in Maryland associated with extreme precipitation events.

Conclusions
Overall, our study suggests a stronger association between extreme precipitation events, compared to extreme heat, and salmonellosis across multiple U.S. regions. In addition, the rates of infection with Salmonella serovars that persist in environmental or plant-based reservoirs, such as S. Javiana and S. Newport, appear to be of particular significance regarding increased heat and rainfall events.
Comparison of false-discovery rates of various decoy databases
Authors: Lee Sangjeong , Park Heejin , Kim Hyunwoo 
Published: September 2021

Abstract
Background
The target-decoy strategy effectively estimates the false-discovery rate (FDR) by creating a decoy database with a size identical to that of the target database. Decoy databases are created by various methods, such as, the reverse, pseudo-reverse, shuffle, pseudo-shuffle, and the de Bruijn methods. FDR is sometimes over- or under-estimated depending on which decoy database is used because the ratios of redundant peptides in the target databases are different, that is, the numbers of unique (non-redundancy) peptides in the target and decoy databases differ.

Results
We used two protein databases (the UniProt Saccharomyces cerevisiae protein database and the UniProt human protein database) to compare the FDRs of various decoy databases. When the ratio of redundant peptides in the target database is low, the FDR is not overestimated by any decoy construction method. However, if the ratio of redundant peptides in the target database is high, the FDR is overestimated when the (pseudo) shuffle decoy database is used. Additionally, human and S. cerevisiae six frame translation databases, which are large databases, also showed outcomes similar to that from the UniProt human protein database.

Conclusion
The FDR must be estimated using the correction factor proposed by Elias and Gygi or that by Kim et al. when (pseudo) shuffle decoy databases are used.
Clinical outcomes and effect on intraoperative blood loss and postoperative pain of patients undergoing retroperitoneal laparoscopic partial nephrectomy for complex renal tumors
Authors: Guo Yansong , Xu Qian , Chen Baochun , Liu Lifeng , Wang Yuanyuan , Zhu Ai , Tian Longjiang 
Published: September 2021

Abstract
Objective
To explore the clinical outcomes and effect on intraoperative blood loss and postoperative pain of patients undergoing the retroperitoneal laparoscopic partial nephrectomy (RLPN) for complex renal tumors.

Methods
Fifty patients with complex renal tumor admitted to our hospital from February 2017 to February 2019 were selected as the research object and divided into the RLPN group (given the retroperitoneal laparoscopic partial nephrectomy, n = 24) and the OPN group (given the open partial nephrectomy, n = 26) by number table method to compare their various perioperative indicators and serum stress response and analyze the clinical effect of different surgical methods on the complex renal tumor.

Results
The clinical information of patients in both groups were not significantly different (P > 0.05); in addition to the operative time, the intraoperative blood loss, hospital stay, warm ischemia time, and numerical rating scale (NRS) scores of the RLPN group were clearly lower than those of the OPN group (P < 0.05); after treatment, patients in the RLPN group obtained significantly lower white blood cell (WBC) count, cortisol, and c-reactive protein (CRP) levels than the OPN group (P < 0.05); the renal glomerular filtration rate (GFR) of the affected side, quality of life scores, and 3-year overall survival rate of treated patients in the RLPN group were obviously higher than those in the OPN group (P < 0.05); and patients in the RPLN group had significantly lower incidence rate (P < 0.05).

Conclusion
Compared with OPN, RLPN is more worthy of promotion and application, because it has better treatment outcomes, significantly reduces intraoperative blood loss, alleviates the body stress response and postoperative pain, and improves the quality of life.
Higher preconceptional maternal body mass index is associated with faster early preimplantation embryonic development: the Rotterdam periconception cohort
Authors: van Duijn Linette , Rousian Melek , Hoek Jeffrey , Willemsen Sten P. , van Marion Eva S. , Laven Joop S. E. , Baart Esther B. , Steegers-Theunissen Régine P. M. 
Published: September 2021

AbstractBackgroundOverweight and obesity affect millions of people globally, which has also serious implications for reproduction. For example, treatment outcomes after in vitro fertilisation (IVF) are worse in women with a high body mass index (BMI). However, the impact of maternal BMI on embryo quality is inconclusive. Our main aim is to study associations between preconceptional maternal BMI and morphokinetic parameters of preimplantation embryos and predicted implantation potential. In addition, associations with clinical IVF outcomes are investigated.MethodsFrom a tertiary hospital, 268 women undergoing IVF or IVF with intracytoplasmic sperm injection (ICSI) were included; 143 normal weight, 79 overweight and 46 obese women. The embryos of these women were cultured in the EmbryoScope, a time-lapse incubator. The morphokinetic parameters of preimplantation embryos and predicted implantation potential, assessed by the KIDScore algorithm were longitudinally evaluated as primary and secondary outcomes, respectively. The tertiary outcomes included clinical outcomes, i.e., fertilization, implantation and live birth rate.ResultsAfter adjustment for patient- and treatment-related factors, we demonstrated in 938 embryos that maternal BMI is negatively associated with the moment of pronuclear appearance (βtPNa-0.070 h (95%CI -0.139, -0.001),p = 0.048), pronuclear fading (βtPNf-0.091 h (95%CI -0.180, -0.003),p = 0.043 and the first cell cleavage (βt2-0.111 h (95%CI -0.205, -0.016),p = 0.022). Maternal BMI was not significantly associated with the KIDScore and tertiary clinical treatment outcomes. In embryos from couples with female or combined factor subfertility, the impact of maternal BMI was even larger (βtPNf-0.170 h (95%CI -0.293, -0.047),p = 0.007; βt2-0.199 h (95%CI -0.330, -0.067),p = 0.003). Additionally, a detrimental impact of BMI per point increase was observed on the KIDScore (β -0.073 (se 0.028),p = 0.010).ConclusionsHigher maternal BMI is associated with faster early preimplantation development. In couples with female or combined factor subfertility, a higher BMI is associated with a lower implantation potential as predicted by the KIDScore. Likely due to power issues, we did not observe an impact on clinical treatment outcomes. However, an effect of faster preimplantation development on post-implantation development is conceivable, especially since the impact of maternal BMI on pregnancy outcomes has been widely demonstrated.
The ameliorative effect of ellagic acid on di-(2-ethylhexyl) phthalate-induced testicular structural alterations, oxidative stress, inflammation and sperm damages in adult mice
Authors: Hosseinzadeh Azam , Mehrzadi Saeed , Siahpoosh Amir , Basir Zahra , Bahrami Nosrat , Goudarzi Mehdi 
Published: September 2021

Abstract
Background
Phthalates such as di (2-ethylhexyl) phthalate (DEHP) are well known exogenous substances, disrupting reproductive system function and structure. The current research demonstrated the effect of ellagic acid (EA) on DEHP-induced testicular injury in mice.

Methods
Thirty-five healthy adult male mice were randomly divided to five groups; normal saline receiving group, DEHP (2 g/kg/day, dissolved in corn oil, p.o.) receiving group, DEHP (2 g/kg/day, dissolved in corn oil, p.o.) and EA receiving groups (25, 50 and 100 mg/kg/day, p.o.). Treatment duration of animals was 14 days. Body and testes weights and sperm characteristics and histological changes of testes were evaluated. Serum testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were analyzed. In the testicular tissue, oxidative/nitrosative stress markers and inflammatory cytokine levels were measured.

Results
Ellagic acid significantly reduced DEHP-induced reduction of body and testes weights. The DEHP-induced reduction of spermatogonia, primary spermatocyte and sertoli cells numbers as well as reduction of sperm vitality and progressive motility were reversed by EA. Furthermore, EA inhibited DEHP-induced alterations in serum hormone levels. These effects were associated with the reduction of DEHP-induced increased level of oxidative stress and inflammatory responses.

Conclusions
Ellagic acid considerably inhibits testicular toxicity of DEHP through reducing oxidative/nitrosative stress and inflammatory responses. Our data suggest that EA may be considered as a promising agent to inhibit male reproductive toxicity induced by endocrine disrupting chemicals such as DEHP.
The CNS-penetrant soluble guanylate cyclase stimulator CYR119 attenuates markers of inflammation in the central nervous system
Authors: Correia Susana S. , Liu Guang , Jacobson Sarah , Bernier Sylvie G. , Tobin Jenny V. , Schwartzkopf Chad D. , Atwater Emily , Lonie Elisabeth , Rivers Sam , Carvalho Andrew , Germano Peter , Tang Kim , Iyengar Rajesh R. , Currie Mark G. , Hadcock John R. , Winrow Christopher J. , Jones Juli E. 
Published: September 2021

Abstract
Background
Inflammation in the central nervous system (CNS) is observed in many neurological disorders. Nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate (NO–sGC–cGMP) signaling plays an essential role in modulating neuroinflammation. CYR119 is a CNS-penetrant sGC stimulator that amplifies endogenous NO–sGC–cGMP signaling. We evaluated target engagement and the effects of CYR119 on markers of neuroinflammation in vitro in mouse microglial cells and in vivo in quinolinic acid (QA)-induced and high-fat diet-induced rodent neuroinflammation models.

Methods
Target engagement was verified in human embryonic kidney (HEK) cells, rat primary neurons, mouse SIM-A9 cells, and in rats by measuring changes in cGMP and downstream targets of sGC signaling [phosphorylated vasodilator-stimulated phosphoprotein (pVASP), phosphorylated cAMP-response element binding (pCREB)]. In SIM-A9 cells stimulated with lipopolysaccharides (LPS), markers of inflammation were measured when cells were treated with or without CYR119. In rats, microinjections of QA and vehicle were administered into the right and left hemispheres of striatum, respectively, and then rats were dosed daily with either CYR119 (10 mg/kg) or vehicle for 7 days. The activation of microglia [ionized calcium binding adaptor molecule 1 (Iba1)] and astrocytes [glial fibrillary acidic protein (GFAP)] was measured by immunohistochemistry. Diet-induced obese (DIO) mice were treated daily with CYR119 (10 mg/kg) for 6 weeks, after which inflammatory genetic markers were analyzed in the prefrontal cortex.

Results
In vitro, CYR119 synergized with exogenous NO to increase the production of cGMP in HEK cells and in primary rat neuronal cell cultures. In primary neurons, CYR119 stimulated sGC, resulting in accumulation of cGMP and phosphorylation of CREB, likely through the activation of protein kinase G (PKG). CYR119 attenuated LPS-induced elevation of interleukin 6 (IL-6) and tumor necrosis factor (TNF) in mouse microglial cells. Following oral dosing in rats, CYR119 crossed the blood–brain barrier (BBB) and stimulated an increase in cGMP levels in the cerebral spinal fluid (CSF). In addition, levels of proinflammatory markers associated with QA administration or high-fat diet feeding were lower in rodents treated with CYR119 than in those treated with vehicle.

Conclusions
These data suggest that sGC stimulation could provide neuroprotective effects by attenuating inflammatory responses in nonclinical models of neuroinflammation.
Serious physical assault and subsequent risk for rehospitalization in individuals with severe mental illness: a nationwide, register-based retrospective cohort study
Authors: Mlada Karolina , Formanek Tomas , Vevera Jan , Latalova Klara , Winkler Petr , Volavka Jan 
Published: September 2021

Abstract
Background
Victimization is associated with worse social and clinical outcomes of individuals with severe mental illness (SMI). A relapse of SMI may be one of the clinical consequences of assaultive trauma. As far as we know, there is no published study that analyzes nationwide health registers to assess the risk of SMI rehospitalization following assault.

Aim
We aimed to assess whether exposure to assault is associated with an increased risk of psychiatric hospitalization in those with SMI.

Methods
We utilized data from the Czech nationwide registers of all-cause hospitalizations and all-cause deaths. We defined exposed individuals as those discharged from a hospitalization for SMI between 2002 and 2007, and hospitalized for serious injuries sustained in an assault in the subsequent 7 years. For each assaulted individual, we randomly selected five counterparts, matched on SMI diagnosis, age and sex, who were not assaulted in the examined time period. We used mixed effect logistic regression to assess the effect of assault on the risk of SMI rehospitalization within the following 6 months. We fitted unadjusted models and models adjusted for the number of previous SMI hospitalizations and drug use disorders.

Results
The sample consisted of 248 exposed and 1 240 unexposed individuals. In the unadjusted model, assaulted individuals were almost four times more likely to be rehospitalized than their non-assaulted counterparts (odds ratio (OR) = 3.96; 95% CI 2.75; 5.71). After adjusting for all covariates, the OR remained threefold higher (OR = 3.07; 95% CI 2.10; 4.49).

Conclusion
People with a history of SMI hospitalization were approximately three times more likely to be rehospitalized for SMI within 6 months after an assault than their non-assaulted SMI counterparts. Soon after a person with SMI is physically assaulted, there should be a psychiatric evaluation and a close follow-up.
Safety of transanal ileal pouch-anal anastomosis for ulcerative colitis: a retrospective observational cohort study
Authors: Lask Aina , Biebl Matthias , Dittrich Luca , Fischer Andreas , Adler Andreas , Tacke Frank , Aigner Felix , Schmuck Rosa , Chopra Sascha , Knoop Michael , Pratschke Johann , Gül-Klein Safak 
Published: September 2021

Abstract
Background
Colectomy with transanal ileal pouch-anal anastomosis (taIPAA) is a surgical technique that can be used to treat benign colorectal disease. Ulcerative colitis is the most frequent inflammatory bowel disease (IBD) and although pharmacological therapy has improved, colectomy rates reach up to 15%. The objective of this study was to determine anastomotic leakage rates and treatment after taIPAA as well as short- and long-term pouch function.

Methods
We conducted a retrospective analysis of a prospective database of all patients undergoing taIPAA at an academic tertiary referral center in Germany, between 01/03/2015 and 31/08/2019. Patients with indications other than ulcerative colitis or with adjuvant chemotherapy following colectomy for colorectal carcinoma were excluded for short- and long-term follow up due to diverging postoperative care yet considered for evaluation of anastomotic leakage.

Results
A total of 22 patients undergoing taIPAA during the study time-window were included in analysis. Median age at the time of surgery was 32 ± 12.5 (14–54) years. Two patients developed an anastomotic leakage at 11 days (early anastomotic leakage) and 9 months (late anastomotic leakage) after surgery, respectively. In both patients, pouches could be preserved with a multimodal approach. Twenty patients out of 22 met the inclusion criteria for short and long term follow-up. Data on short-term pouch function could be obtained in 14 patients and showed satisfactory pouch function with only four patients reporting intermittent incontinence at a median stool frequency of 9–10 times per day. In the long-term we observed an inflammation or “pouchitis” in 11 patients and a pouch failure in one patient.

Conclusion
Postoperative complication rates in patients with benign colorectal disease remain an area of concern for surgical patient safety. In this pilot study on 22 selected patients, taIPAA was associated with two patients developing anastomotic leakage. Future large-scale validation studies are required to determine the safety and feasibility of taIPAA in patients with ulcerative colitis.
Are we sure that the neurological impact of COVID 19 in childhood has not been underestimated?
Authors: Principi Nicola , Esposito Susanna 
Published: September 2021

Abstract
Background
Presently, it is known that, even if less frequently than in adults, children can develop a severe new coronavirus disease 2019 (COVID-19). Children with the SARS-CoV-2 infection can have neurological signs and symptoms of disease more frequently than previously thought, revealing the involvement of the central nervous system, the peripheral nervous system, or both. Aim of this manuscript is to highlight the neurologic complications associated with SARS-CoV-2 among pediatric patients with COVID-19, suggesting when to monitor carefully neurologic development.

Main findings
Children with a severe chronic underlying disease, infants and toddlers and those who develop the so-called multisystem inflammatory syndrome (MIS-C) are those with the highest incidence of neurological complications. Fortunately, in most of the cases, neurological manifestations, mainly represented by headache and anosmia, are mild and transient and do not significantly complicate the COVID-19 course. However, in some cases, very severe clinical problems associated with relevant alterations of neuroimaging, electroencephalography, nerve conduction studies and electromyography findings can develop. Generally, almost all the children with COVID-19 and neurological manifestations till now described have made a complete recovery, although in some cases this has occurred after several weeks of treatment. Moreover, COVID-19 infection during pregnancy has been found associated with an increased risk of obstetric complications that can lead to neurological acute and long-term manifestations in neonates.

Conclusions
Based on data showing the neurologic impact of COVID-19 in pediatric age, we suggest monitoring neurological development a few months after healing in pediatric patients who have presented MIS-C, seizures or other neurological manifestations and in children of pregnant women with COVID-19 in order to detect overt and subtle deficits.