bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pembrolizumab, radiotherapy, and an immunomodulatory five-drug cocktail in pretreated patients with persistent, recurrent, or metastatic cervical or endometrial carcinoma: Results of the phase II PRIMMO study
Authors: De Jaeghere Emiel A. , Tuyaerts Sandra , Van Nuffel An M. T. , Belmans Ann , Bogaerts Kris , Baiden-Amissah Regina , Lippens Lien , Vuylsteke Peter , Henry Stéphanie , Trinh Xuan Bich , van Dam Peter A. , Aspeslagh Sandrine , De Caluwé Alex , Naert Eline , Lambrechts Diether , Hendrix An , De Wever Olivier , Van de Vijver Koen K. , Amant Frédéric , Vandecasteele Katrien , Denys Hannelore G. 
Published: August 2022

AbstractA phase II study (PRIMMO) of patients with pretreated persistent/recurrent/metastatic cervical or endometrial cancer is presented. Patients received an immunomodulatory five-drug cocktail (IDC) consisting of low-dose cyclophosphamide, aspirin, lansoprazole, vitamin D, and curcumin starting 2 weeks before radioimmunotherapy. Pembrolizumab was administered three-weekly from day 15 onwards; one of the tumor lesions was irradiated (8Gyx3) on days 15, 17, and 19. The primary endpoint was the objective response rate per immune-related response criteria (irORR) at week 26 (a lower bound of the 90% confidence interval [CI] of > 10% was considered efficacious). The prespecified 43 patients (cervical, n = 18; endometrial, n = 25) were enrolled. The irORR was 11.1% (90% CI 2.0–31.0) in cervical cancer and 12.0% (90% CI 3.4–28.2) in endometrial cancer. Median duration of response was not reached in both cohorts. Median interval-censored progression-free survival was 4.1 weeks (95% CI 4.1–25.7) in cervical cancer and 3.6 weeks (95% CI 3.6–15.4) in endometrial cancer; median overall survival was 39.6 weeks (95% CI 15.0–67.0) and 37.4 weeks (95% CI 19.0–50.3), respectively. Grade ≥ 3 treatment-related adverse events were reported in 10 (55.6%) cervical cancer patients and 9 (36.0%) endometrial cancer patients. Health-related quality of life was generally stable over time. Responders had a significantly higher proportion of peripheral T cells when compared to nonresponders (p = 0.013). In conclusion, PRIMMO did not meet its primary objective in both cohorts; pembrolizumab, radiotherapy, and an IDC had modest but durable antitumor activity with acceptable but not negligible toxicity.Trial registration ClinicalTrials.gov (identifier NCT03192059) and EudraCT Registry (number 2016-001569-97).
Stability-instability transition in tripartite merged ecological networks
Authors: Emary Clive , Malchow Anne-Kathleen 
Published: August 2022

AbstractAlthough ecological networks are typically constructed based on a single type of interaction, e.g. trophic interactions in a food web, a more complete picture of ecosystem composition and functioning arises from merging networks of multiple interaction types. In this work, we consider tripartite networks constructed by merging two bipartite networks, one mutualistic and one antagonistic. Taking the interactions within each sub-network to be distributed randomly, we consider the stability of the dynamics of the network based on the spectrum of its community matrix. In the asymptotic limit of a large number of species, we show that the spectrum undergoes an eigenvalue phase transition, which leads to an abrupt destabilisation of the network as the ratio of mutualists to antagonists is increased. We also derive results that show how this transition is manifest in networks of finite size, as well as when disorder is introduced in the segregation of the two interaction types. Our random-matrix results will serve as a baseline for understanding the behaviour of merged networks with more realistic structures and/or more detailed dynamics.
Involvement of glutamine synthetase 2 (GS2) amplification and overexpression in Amaranthus palmeri resistance to glufosinate
Authors: Noguera Matheus M. , Porri Aimone , Werle Isabel S. , Heiser James , Brändle Frank , Lerchl Jens , Murphy Brent , Betz Michael , Gatzmann Fanny , Penkert Martin , Tuerk Clara , Meyer Lucie , Roma-Burgos Nilda 
Published: August 2022

Abstract
Main conclusion
Amplification and overexpression of the target site glutamine synthetase, specifically the plastid-located isoform, confers resistance to glufosinate in Amaranthus palmeri. This mechanism is novel among glufosinate-resistant weeds.

Abstract
Amaranthus palmeri has recently evolved resistance to glufosinate herbicide. Several A. palmeri populations from Missouri and Mississippi, U.S.A. had survivors when sprayed with glufosinate-ammonium (GFA, 657 g ha−1). One population, MO#2 (fourfold resistant) and its progeny (sixfold resistant), were used to study the resistance mechanism, focusing on the herbicide target glutamine synthetase (GS). We identified four GS genes in A. palmeri; three were transcribed: one coding for the plastidic protein (GS2) and two coding for cytoplasmic isoforms (GS1.1 and GS1.2). These isoforms did not contain mutations associated with resistance. The 17 glufosinate survivors studied showed up to 21-fold increase in GS2 copies. GS2 was expressed up to 190-fold among glufosinate survivors. GS1.1 was overexpressed > twofold in only 3 of 17, and GS1.2 in 2 of 17 survivors. GS inhibition by GFA causes ammonia accumulation in susceptible plants. Ammonia level was analyzed in 12 F1 plants. GS2 expression was negatively correlated with ammonia level (r =  – 0.712); therefore, plants with higher GS2 expression are less sensitive to GFA. The operating efficiency of photosystem II (ϕPSII) of Nicotiana benthamiana overexpressing GS2 was four times less inhibited by GFA compared to control plants. Therefore, increased copy and overexpression of GS2 confer resistance to GFA in A. palmeri (or other plants). We present novel understanding of the role of GS2 in resistance evolution to glufosinate.
The SNARC effect: a preregistered study on the interaction of horizontal, vertical, and sagittal spatial–numerical associations
Authors: Aleotti Sara , Massaccesi Stefano , Priftis Konstantinos 
Published: August 2022

AbstractSmall numbers are processed faster through left-sided than right-sided responses, whereas large numbers are processed faster through right-sided than left-sided responses [i.e., the Spatial–Numerical Association of Response Codes (SNARC) effect]. This effect suggests that small numbers are mentally represented on the left side of space, whereas large numbers are mentally represented on the right side of space, along a mental number line. The SNARC effect has been widely investigated along the horizontal Cartesian axis (i.e., left–right). Aleotti et al. (Cognition 195:104111, 2020), however, have shown that the SNARC effect could also be observed along the vertical (i.e., small numbers-down side vs. large numbers-up side) and the sagittal axis (i.e., small numbers-near side vs. large numbers-far side). Here, we investigated whether the three Cartesian axes could interact to elicit the SNARC effect. Participants were asked to decide whether a centrally presented Arabic digit was odd or even. Responses were collected through an ad hoc-made response box on which the SNARC effect could be compatible for one, two, or three Cartesian axes. The results showed that the higher the number of SNARC-compatible Cartesian axes, the stronger the SNARC effect. We suggest that numbers are represented in a three-dimensional number space defined by interacting Cartesian axes.
Splenic artery embolization changes the management of blunt splenic injury: an observational analysis of 680 patients graded by the revised 2018 AAST-OIS
Authors: Lin Being-Chuan , Wu Cheng-Hsien , Wong Yon-Cheong , Chen Huan-Wu , Fu Chen-Ju , Huang Chen-Chih , Wu Chen-Te , Hsieh Chi-Hsun 
Published: August 2022

Abstract
Background
This study aimed to evaluate the management of blunt splenic injury (BSI) and highlight the role of splenic artery embolization (SAE).

Methods
We conducted a retrospective review of all patients with BSI over 15 years. Splenic injuries were graded by the 2018 revision of the American Association for the Surgery of Trauma-Organ Injury Scale (AAST-OIS). Our hospital provide 24/7 in-house surgeries and 24/7 in-house interventional radiology facility. Patients with BSI who arrived hypotensive and were refractory to resuscitation required surgery and patients with vascular injury on abdominal computed tomography were considered for SAE.

Results
In total, 680 patients with BSI, the number of patients who underwent nonoperative management with observation (NOM-obs), SAE, and surgery was 294, 234, and 152, respectively. The number of SAEs increased from 4 (8.3%) in 2001 to 23 (60.5%) in 2015 (p < 0.0001); conversely, the number of surgeries decreased from 21 (43.8%) in 2001 to 4 (10.5%) in 2015 (p = 0.001). The spleen-related mortality rate of NOM-obs, SAEs, and surgery was 0%, 0.4%, and 7.2%, respectively. In the SAE subgroup, according to the 2018 AAST-OIS, 234 patients were classified as grade II, n = 3; III, n = 21; IV, n = 111; and V, n = 99, respectively.; and compared with 1994 AST-OIS, 150 patients received a higher grade and the total number of grade IV and V injuries ranged from 96 (41.0%) to 210 (89.7%) (p < 0.0001). On angiography, 202 patients who demonstrated vascular injury and 187 achieved hemostasis after SAE with a 92.6% success rate. Six of the 15 patients failed to SAE preserved the spleen after second embolization with a 95.5% salvage rate.

Conclusions
Our data confirm the superiority of the 2018 AAST-OIS and support the role of SAE in changing the trend of management of BSI.

Graphical abstract
Long-term results of minimally invasive transanal surgery for rectal tumors in 249 consecutive patients
Authors: Maeda Kotaro , Koide Yoshikazu , Katsuno Hidetoshi , Tajima Yosuke , Hanai Tsunekazu , Masumori Koji , Matsuoka Hiroshi , Shiota Miho 
Published: August 2022

Abstract
Purpose
To delineate the long-term results of minimally invasive transanal surgery (MITAS) for selected rectal tumors.

Methods
We analyzed data, retrospectively, on consecutive patients who underwent MITAS between 1995 and 2015, to establish the feasibility, excision quality, and perioperative and oncological outcomes of this procedure.

Results
MITAS was performed on 243 patients. The final histology included 142 cancers, 47 adenomas, and 52 neuroendocrine tumors (NET G1). A positive margin of 1.6% and 100% en bloc resection were achieved. The mean operative time was 27.4 min. Postoperative morbidity occurred in 7% of patients, with 0% mortality. The median follow-up was 100 months (up to ≥ 5 years or until death in 91.8% of patients). Recurrence developed in 2.9% of the patients. The 10-year overall survival rate was 100% for patients with NET G1 and 80.3% for those with cancer. The 5-year DFS was 100% for patients with Tis cancer, 90.6% for those with T1 cancer, and 87.5% for those with T2 or deeper cancers. MITAS for rectal tumors ≥ 3 cm resulted in perioperative and oncologic outcomes equivalent to those for tumors < 3 cm.

Conclusion
MITAS is feasible for the local excision (LE) of selected rectal tumors, including tumors ≥ 3 cm. It reduces operative time and secures excision quality and long-term oncological outcomes.
The riskiness of stock versus money market investment with stochastic rates
Authors: Szabó Dávid Zoltán , Bihary Zsolt 
Published: August 2022

AbstractTo efficiently assess the performance of investing in stocks rather than in a bank account for the long run, stochastic interest rate modelling is advocated. We introduce a correlated stochastic interest rate model that addresses this problem. We derive analytic formulas for general spectral risk measures in our setting, and apply our results to Value at Risk, Expected Shortfall and GlueVaR. We characterize the short- and long-term behaviour of these risk measures. We fit our model to financial markets, perform an empirical study and evaluate risk numbers for realistic scenarios in the future. Our results reveal sizeable sensitivities on parameter estimation, but we may conclude that holding stocks for less than a few decades bears significant risk.
Health and labor force participation among older workers in Switzerland: a growth curve analysis
Authors: Feer Sonja , Lipps Oliver , Dratva Julia , Baumann Isabel 
Published: August 2022

AbstractThis study investigated how individual trajectories of self-rated health (SRH) and working hours among older workers in Switzerland are interrelated and how this relationship varies based on occupation. We used data from the Swiss Household Panel to analyze the long-term trajectories of older workers measured in terms of working hours and SRH. The sample included more than 4000 workers aged 50 to 65(men)/64(women). We ran a bivariate response multilevel model for growth that allowed the examination of between- and within-individual changes over time. On a between-individual level, we found that the upper non-manual workers were the most heterogeneous occupational group in terms of working hours and the lower non-manual workers were the most heterogeneous occupational group in terms of health. Within all occupational groups, we found a significant relationship between the level of working hours and level of SRH. The individual-level statistics showed consistently strongest effects for manual workers. This result confirms our hypothesis that labor force participation in individuals of the manual occupational group is more sensitive to their health status. Our findings contribute to the debate regarding the importance of older workers’ health in the context of the extension of working life.
Inventing Engineered Organoids for end-stage liver failure patients
Authors: Antarianto Radiana D , Mahmood Amer , Giselvania Angela , Asri Dewi Ayu AA Prima , Gustinanda Jatmiko , Pawitan Jeanne Adiwinata 
Published: August 2022

AbstractEnd-stage liver disease (ESLD) is a term used clinically in reference to a group of liver diseases with liver transplantation as the choice of treatment. Due to the limitations of liver transplantation, alternative treatments are needed. The use of primary human hepatocytes represents a valid alternative treatment, but the limitations related to hepatocyte quality, viability, function, conservation, and storage need to be overcome. Transplanted hepatocytes have only been followed for 6–9 months. Therefore, long-term causes of failures are not yet established, including rejection, apoptosis, or other causes. Other alternative therapies to replace liver transplantation include plasmapheresis, hemodiafiltration, and artificial livers. Unfortunately, these methods are highly limited due to availability, high cost, anaphylaxis reaction, development-deposition of immune-complexes, and restricted functionality. Liver organoids, which utilize stem cells instead of ‘impractical’ adult hepatocytes, may be a solution for the development of a complex bioartificial liver. Recent studies have explored the benefits of differentiating mature hepatocytes from stem cells inside a bioreactor. When the use of human-induced Hepatocytes (hiHeps) was investigated in mouse and pig models of liver failure, liver failure markers were decreased, hepatocyte function indicated by albumin synthesis improved, and survival time increased. Bioartificial liver treatment may decrease the infiltration of inflammatory cells into liver tissue by down-regulating pro-inflammatory cytokines.
Identification of novel proteins involved in P2X7-mediated signaling cascades
Authors: Sassenbach Lukas 
Published: August 2022

AbstractHigh concentration of extracellular ATP acts as a danger signal that is sensed by the P2X7 receptor (P2X7R). This ATP-gated ion channel has been shown to induce multiple metabotropic events such as changes in plasma membrane composition and morphology, ectodomain shedding, activation of lipases, kinases, and transcription factors as well as cytokine release. The specific signaling pathways and molecular mechanisms remain largely obscure. Using an unbiased genome-scale CRISPR/Cas9 screening approach in a murine T cell line, Ryoden et al. (2022, 2020) identified three proteins involved in P2X7 regulation and signaling: Essential for Reactive Oxygen Species (EROS) is essential for P2X7 folding and maturation, and Xk and Vsp13a are required for P2X7-mediated phosphatidyl serine exposure and cell lysis. They further provide evidence for an interaction of Xk and Vsp13a at the plasma membrane and confirm the role of Xk in ATP-induced cytolysis in primary CD25+CD4+ T cells from Xk−/− mice.
Blended-eLearning Improves Alcohol Use Care in Kenya: Pragmatic Randomized Control Trial Results and Parallel Qualitative Study Implications
Authors: Clair Veronic , Musau Abednego , Mutiso Victoria , Tele Albert , Atkinson Katlin , Rossa-Roccor Verena , Bosire Edna , Ndetei David , Frank Erica 
Published: August 2022

Abstract
Alcohol use is the 5th most important risk factor contributing to the global burden of diseases, with stigma and a lack of trained health workers as the main barriers to adequate care. This study assesses the impact of providing blended-eLearning courses teaching the alcohol, smoking, and substance involvement screening test (ASSIST) screening and its linked brief intervention (BI). In public and private facilities, two randomized control trials (RCTs) showed large and similar decreases in alcohol use in those receiving the BI compared to those receiving only the ASSIST feedback. Qualitative findings confirm a meaningful reduction in alcohol consumption; decrease in stigma and significant practice change, suggesting lay health workers and clinicians can learn effective interventions through blended-eLearning; and significantly improve alcohol use care in a low- and middle-income country (LMIC) context. In addition, our study provides insight into why lay health workers feedback led to a similar decrease in alcohol consumption compared to those who also received a BI by clinicians.
Extreme heavy metal and blasphemy in Iran: the case of Confess
Authors: Eckerström Pasqualina 
Published: August 2022

AbstractSince the revolution in 1979, the Islamic Republic of Iran has imprisoned musicians, especially punk, hip-hop, and hard rock bands, as well as those playing heavy metal subgenres. Extreme heavy metal artists and fans emerged in the 1990s. The government soon targeted them as Satanists and began a systematic crackdown on metalheads. The metalcore band Confess is the most well-known case. The band was arrested in 2015 on counts of blasphemy, disturbing public opinion through the production of music, participating in interviews with the opposition media and propaganda against the Islamic Republic of Iran, among other charges. The majority of secular countries today do not consider extreme heavy metal to be transgressive. This is not the case in contexts where religious traditions have a significant influence on society. By analysing the narrative of the band Confess, the purpose of this paper is to provide an understanding of how Iranian extreme metal musicians resist religious oppression, challenge their government, religious precepts, and social values through their music.
Forecasting the Potential Effects of Climate Change on Malaria in the Lake Victoria Basin Using Regionalized Climate Projections
Authors: Ototo Ednah N. , Ogutu Joseph O. , Githeko Andrew , Said Mohammed Y. , Kamau Lucy , Namanya Didacus , Simiyu Stella , Mutimba Stephen 
Published: August 2022

Abstract
Background
Malaria epidemics are increasing in East Africa since the 1980s, coincident with rising temperature and widening climate variability. A projected 1–3.5 °C rise in average global temperatures by 2100 could exacerbate the epidemics by modifying disease transmission thresholds. Future malaria scenarios for the Lake Victoria Basin (LVB) are quantified for projected climate scenarios spanning 2006–2100.

Methods
Regression relationships are established between historical (1995–2010) clinical malaria and anaemia cases and rainfall and temperature for four East African malaria hotspots. The vector autoregressive moving average processes model, VARMAX (p,q,s), is then used to forecast malaria and anaemia responses to rainfall and temperatures projected with an ensemble of eight General Circulation Models (GCMs) for climate change scenarios defined by three Representative Concentration Pathways (RCPs 2.6, 4.5 and 8.5).

Results
Maximum temperatures in the long rainy (March–May) and dry (June–September) seasons will likely increase by over 2.0 °C by 2070, relative to 1971–2000, under RCPs 4.5 and 8.5. Minimum temperatures (June–September) will likely increase by over 1.5–3.0 °C under RCPs 2.6, 4.5 and 8.5. The short rains (OND) will likely increase more than the long rains (MAM) by the 2050s and 2070s under RCPs 4.5 and 8.5. Historical malaria cases are positively and linearly related to the 3–6-month running means of monthly rainfall and maximum temperature. Marked variation characterizes the patterns projected for each of the three scenarios across the eight General Circulation Models, reaffirming the importance of using an ensemble of models for projections.

Conclusions
The short rains (OND), wet season (MAM) temperatures and clinical malaria cases will likely increase in the Lake Victoria Basin. Climate change adaptation and mitigation strategies, including malaria control interventions could reduce the projected epidemics and cases. Interventions should reduce emerging risks, human vulnerability and environmental suitability for malaria transmission.
Long-Term Outcomes of Laparoscopic Gastric Plication for Treatment of Morbid Obesity: a Single-Center Experience
Authors: Abdelgawad Mohamed , Elgeidie Ahmed , Sorogy Mohamed El , Elrefai Mohamed , Hamed Hosam , El-Magd El-Sayed Abou 
Published: August 2022

Abstract
Background
Although laparoscopic gastric plication (LGP) has been mentioned in many studies, its practice has not yet been standardized. In addition, the outcomes remain conflicting, especially long-term ones. This study was conducted to elucidate the long-term consequences of LGP.

Methods
Retrospective analysis of patients with obesity underwent LGP at our institution between March 2010 and September 2014. Data were prospectively collected from our database.

Results
Of the 88 consecutive patients in the study period between 2010 and 2014, follow-up data out to 6 years was available in 60 LGP patients (68.18%). The mean age of the included patients was 41.3 ± 10 years. A total of 81.7% were females. We observed a significant BMI reduction out to 2 years (p < 0.001), a plateau at 3 and 4 years, and a significant BMI increase at 6 years (p < 0.01). %TWL at 2 years was 21.14% and 12.08% at 6 years. Weight regain was observed in 35 patients at 6 years to reach a rate of 58.3%. Predictors for weight regain at 6 years were disrupted plication fold, increased hunger, and non-adherence to regular exercise. The diabetes improvement rate was 66.6% at 6 years. There were 14 re-operations (23.3%): 1 emergency (1.6%) and 13 (21.6%) elective. There was no mortality.

Conclusion
At the 6-year follow-up visit, LGP has a much less durable effect on weight loss with a % EWL of 32% and a weight regain of 58.3% resulting in a high rate of revisions.

Graphical abstract