bluuebunny/crossref_metadata_2025_split huggingface dataset:
Different subtypes of nonthyroidal illness syndrome on the prognosis of septic patients: a two-centered retrospective cohort study
Authors: Ning Ning , Li Juan , Sun Wenwu , Ma Chaoping , Li Jiaoyan , Sheng Huiqiu , Chen Ying , Zhao Bing , Zhang Jiyuan , Zhu Jiyue , Gao Chengjin , Mao Enqiang 
Published: September 2023

BackgroundNonthyroidal illness syndrome (NTIS) is a common endocrine dysfunction predicting unfavorable outcomes in critical illness. The objective of the study is to evaluate the association between different NTIS subtypes with outcomes in septic patients.MethodsSeptic patients in two Chinese academic centers from October 2012 and October 2022 are enrolled in analysis. Multivariable regressions are used to assess associations between NTIS and outcomes. Outcomes include in-hospital mortality, length of stay in hospital (LOS), non-invasive ventilation failure and weaning failure. Patients with NTIS are categorized into 4 types according to the different levels of FT4 and TSH. The association between different NTIS subtypes and mortality are further analyzed. Survival curve is plotted using the Kaplan–Meier method.ResultsAfter screening, a total of 1226 septic patients with complete thyroid hormones result are eventually enrolled. Among them, 520 (42.4%) patients are diagnosed as NTIS. In multivariable regression analysis, NTIS is independently associated with increased 30-days mortality (OR=1.759, CI 1.009-3.104, p=0.047), but has no association with 60-days mortality (OR=1.524, CI 0.893-2.618, p=0.123), 90-days mortality (OR=1.411, CI 0.831-2.408, p=0.203), LOS, non-invasive ventilation failure or weaning failure. In NTIS subtypes, NTIS patients with low FT3 and TSH levels, regardless of the FT4 values, have significantly higher mortality than euthyroid patients (30-days mortality, OR= 6.488, CI 1.546-27.808, p=0.01; 60-days mortality, OR=3.973, CI 1.006-15.579, p=0.046; 90-days mortality, OR=3.849, CI 0.977-15.088, p=0.051). This result is consistent in patients with low FT3 and FT4 levels, regardless of the TSH values (30-days mortality, OR=3.349, CI 1.402-7.957, p=0.006; 60-days mortality, OR= 2.594, CI 1.122-5.930, p=0.024; 90-days mortality, OR=2.55, CI 1.110-5.804, p=0.025). There is no survival difference between NTIS patients with low FT3 only and euthyroid patients. Survival plot shows the worst prognosis is in NTIS patients with low FT3, FT4 and TSH level.ConclusionsNTIS is frequent in sepsis. A reduction of FT3 together with FT4 or TSH, but not FT3 only, is associated with an increased risk of mortality.
Evaluation of fuel consumption and emissions benefits of connected and automated vehicles in mixed traffic flow
Authors: Li Honggang , Li Hongtao , Hu Yi , Xia Tong , Miao Qiqi , Chu Jiangwei 
Published: September 2023

Introduction: The presence of connected and automated vehicles (CAV) in mixed traffic flows with different market penetration rates (MPRs) in urban road scenarios has a significant effect on fuel consumption and exhaust emissions.Methods: Therefore, in this study, real-world road networks and traffic data are simulated using SUMO based on actual data from a survey. The fuel consumption and emission benefits of CAVs in mixed traffic flows are well-evaluated, and the energy-saving performance of CAVs under low-speed vehicle interference is tested. In addition, this study explores both the energy consumption and emissions of purely electric vehicles.Results: The results show that with 100% CAV penetration, fuel vehicles have a maximum reduction in fuel consumption of 18% and a maximum increase in average speed of 31.6%, while the energy consumption of electric vehicles increases due to communication, detection, and collaboration between CAVs.Discussion: However, the results clearly demonstrate that the carbon emissions of electric vehicles are significantly lower than fuel vehicles. In addition, the increase in low-speed vehicles will result in an increase in energy consumption and emissions. Therefore, increasing the percentage of electric vehicles on the roads and transitioning from manual to autonomous driving systems is crucial to curbing carbon emissions.
An increasing trend in daily monsoon precipitation extreme indices over Pakistan and its relationship with atmospheric circulations
Authors: Ullah Waheed , Karim Aisha , Ullah Sami , Rehman Atta-Ur , Bibi Tehmina , Wang Guojie , Ullah Safi , Bhatti Asher Samuel , Ali Gohar , Abbas Adnan , Hagan Daniel Fiffi Tawia , Nooni Isaac Kwesi , Zhu Chenxia , Hussain Azfar 
Published: September 2023

This study assessed spatiotemporal trends in daily monsoon precipitation extremes at seasonal and sub-seasonal scales (June, July, August, and September) and their links with atmospheric circulations over Pakistan. The study used observed precipitation data from fifty in-situ stations and reanalysis products from the European Centre for Medium-Range Weather Forecasts (ECMWF) and National Centers for Environmental Prediction/the National Center for Atmospheric Research (NCEP/NCAR) during 1981–2018. A suite of seven extreme precipitation indices and non-parametric statistical techniques were used to infer trends in the frequency and intensity of extreme precipitation indices. An increase in frequency and intensity of overall extreme indices was evident, with a maximum tendency in the country’s northwestern (z-score=&gt;2.5), central, and eastern (z-score &gt; 4) monsoon-dominant parts. The northern and southwestern parts of the country exhibited a slight decrease (z-score &lt;–2) in frequency and intensity. The Sen’s Slope estimator (SSE) shows an increase in western parts (0.20 days) indicating a shift in the maxima of the monsoon precipitation. The regional precipitation shows an increase in wet days (R1 mm) with higher values of mMK (3.71) and SSE (0.3) in region 2 Similar results of moderate regional increase are evident for extreme indices except regions 1 and 3. The extreme 1-day maximum precipitation increased in region 3 (mMK: 1.39, SSE: 2.32). The extremely wet days (R99p TOT) precipitation has a moderate increase in all regions with a decrease in region 1. The temporal mutations showed dynamic changes, clearly reflecting the country’s historical extreme events. The frequency and intensity of precipitation extremes negatively correlated with the altitude (R = −0.00039). The probability density function (PDF) showed a significant increase in the density during June and September with a probabilistic positive shift during July and August. The intensified mid-latitude westerlies and subtropical zonal easterlies teleconnections, strengthening of the monsoon trough, and land-ocean thermal contrast are the potential drivers of the increasing trend in precipitation extremes. The current study could serve as a benchmark for future researchers and policymakers to devise effective mitigation strategies for sustainable development.
Herring roe oil in treatment of psoriasis – influence on immune cells and cytokine network
Authors: Petrovic Aleksandra , Bueide Ingvild , Tveit Kåre Steinar , Hallaråker Hogne , Bjørndal Bodil , Holmes Tim D. , Davies Richard , Brokstad Karl Albert , Bergum Brith , Appel Silke 
Published: September 2023

BackgroundPsoriasis is a chronic immune-mediated skin disease with systemic inflammation and comorbidities. Although the disease severity may vary over time, many patients suffer from mild to moderate disease. Often local treatment will be sufficient to control the symptoms, but they may have several side effects. ω-3 polyunsaturated fatty acids have shown promising results in clinical trials with mild-to-moderate psoriasis.MethodsWe explored the impact of phospholipid bound docosahexaenoic acid and eicosapentaenoic acid in a 3:1 ratio on immune cells and cytokine networks in peripheral blood of patients with psoriasis. We investigated the inter-relation of plasma cytokine levels and disease severity in 58 patients, and explored the status of circulating immune cell activity in 18 patients with non-severe psoriasis before and during herring roe oil supplementation. Plasma concentration of 22 cytokines was measured by Luminex technology and circulating immune cells were analyzed by multicolor flow cytometry.ResultsCCL2 levels decreased over time, and IFN-γR1 increased, possibly related to the action of ω-3 polyunsaturated fatty acids. We observed a shift from naïve to effector CD4+ T cells and decreases of CD38 expression on CD4+ and CD8+ T cells, CD56bright NK cells and CD14+CD16- classical monocytes.ConclusionsThese findings support the beneficial effect of herring roe oil supplementation.
Fibrinolytic potential as a risk factor for postpartum hemorrhage
Authors: Gruneberg Daniel , Braun Paula , Schöchl Herbert , Nachtigall-Schmitt Tereza , von der Forst Maik , Tourelle Kevin , Dietrich Maximilian , Wallwiener Markus , Wallwiener Stephanie , Weigand Markus A. , Fluhr Herbert , Spratte Julia , Hofer Stefan , Schmitt Felix Carl Fabian 
Published: September 2023

BackgroundPostpartum hemorrhage (PPH) is still the leading cause of maternal morbidity and mortality worldwide. While impaired fibrin polymerization plays a crucial role in the development and progress of PPH, recent approaches using viscoelastic measurements have failed to sensitively detect early changes in fibrinolysis in PPH. This study aimed to evaluate whether women experiencing PPH show alterations in POC-VET fibrinolytic potential during childbirth and whether fibrinolytic potential offers benefits in the prediction and treatment of PPH.MethodsBlood samples were collected at three different timepoints: T0 = hospital admission (19 h ± 18 h prepartum), T1 = 30–60 min after placental separation, and T2 = first day postpartum (19 h ± 6 h postpartum). In addition to standard laboratory tests, whole-blood impedance aggregometry (Multiplate) and viscoelastic testing (VET) were performed using the ClotPro system, which included the TPA-test lysis time, to assess the POC-VET fibrinolytic potential, and selected coagulation factors were measured. The results were correlated with blood loss and clinical outcome markers. Severe PPH was defined as a hemoglobin drop &gt; 4g/dl and/or the occurrence of shock or the need for red blood cell transfusion.ResultsBlood samples of 217 parturient women were analyzed between June 2020 and December 2020 at Heidelberg University Women's Hospital, and 206 measurements were eligible for the final analysis. Women experiencing severe PPH showed increased fibrinolytic potential already at the time of hospital admission. When compared to non-PPH, the difference persisted 30–60 min after placental separation. A higher fibrinolytic potential was accompanied by a greater drop in fibrinogen and higher d-dimer values after placental separation. While 70% of women experiencing severe PPH showed fibrinolytic potential, 54% of those without PPH showed increased fibrinolytic potential as well.ConclusionWe were able to show that antepartal and peripartal fibrinolytic potential was elevated in women experiencing severe PPH. However, several women showed high fibrinolytic potential but lacked clinical signs of PPH. The findings indicate that high fibrinolytic potential is a risk factor for the development of coagulopathy, but further conditions are required to cause PPH.
A curated census of pathogenic and likely pathogenic UTR variants and evaluation of deep learning models for variant effect prediction
Authors: Bohn Emma , Lau Tammy T. Y. , Wagih Omar , Masud Tehmina , Merico Daniele 
Published: September 2023

Introduction: Variants in 5′ and 3′ untranslated regions (UTR) contribute to rare disease. While predictive algorithms to assist in classifying pathogenicity can potentially be highly valuable, the utility of these tools is often unclear, as it depends on carefully selected training and validation conditions. To address this, we developed a high confidence set of pathogenic (P) and likely pathogenic (LP) variants and assessed deep learning (DL) models for predicting their molecular effects.Methods: 3′ and 5′ UTR variants documented as P or LP (P/LP) were obtained from ClinVar and refined by reviewing the annotated variant effect and reassessing evidence of pathogenicity following published guidelines. Prediction scores from sequence-based DL models were compared between three groups: P/LP variants acting though the mechanism for which the model was designed (model-matched), those operating through other mechanisms (model-mismatched), and putative benign variants. PhyloP was used to compare conservation scores between P/LP and putative benign variants.Results: 295 3′ and 188 5′ UTR variants were obtained from ClinVar, of which 26 3′ and 68 5′ UTR variants were classified as P/LP. Predictions by DL models achieved statistically significant differences when comparing modelmatched P/LP variants to both putative benign variants and modelmismatched P/LP variants, as well as when comparing all P/LP variants to putative benign variants. PhyloP conservation scores were significantly higher among P/LP compared to putative benign variants for both the 3′ and 5′ UTR.Discussion: In conclusion, we present a high-confidence set of P/LP 3′ and 5′ UTR variants spanning a range of mechanisms and supported by detailed pathogenicity and molecular mechanism evidence curation. Predictions from DL models further substantiate these classifications. These datasets will support further development and validation of DL algorithms designed to predict the functional impact of variants that may be implicated in rare disease.
BACE1 and SCD1 are associated with neurodegeneration
Authors: Bedoya-Guzmán Ferley A. , Pacheco-Herrero Mar , Salomon-Cruz Ivan Daniel , Barrera-Sandoval Angela Maria , Gutierrez Vargas Johanna Andrea , Villamil-Ortiz Javier Gustavo , Villegas Lanau Carlos Andres , Arias-Londoño Julián David , Area-Gomez Estela , Cardona Gomez Gloria Patricia 
Published: September 2023

IntroductionProteolytic processing of amyloid protein precursor by β-site secretase enzyme (BACE1) is dependent on the cellular lipid composition and is affected by endomembrane trafficking in dementia and Alzheimer's disease (AD). Stearoyl-CoA desaturase 1 (SCD1) is responsible for the synthesis of fatty acid monounsaturation (MUFAs), whose accumulation is strongly associated with cognitive dysfunction.MethodsIn this study, we analyzed the relationship between BACE1 and SCD1 in vivo and in vitro neurodegenerative models and their association in familial AD (FAD), sporadic AD (SAD), and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) using microscopy, biochemical, and mass SPECT approach.ResultsOur findings showed that BACE1 and SCD1 immunoreactivities were increased and colocalized in astrocytes of the hippocampus in a rat model of global cerebral ischemia (2-VO). A synergistic effect of double BACE1/SCD1 silencing on the recovery of motor and cognitive functions was obtained. This neuroprotective regulation involved the segregation of phospholipids (PLs) associated with polyunsaturated fatty acids in the hippocampus, cerebrospinal fluid, and serum. The double silencing in the sham and ischemic groups was stronger in the serum, inducing an inverse ratio between total phosphatydilcholine (PC) and lysophosphatidylcholine (LPC), represented mainly by the reduction of PC 38:4 and PC 36:4 and an increase in LPC 16:0 and LPC 18:0. Furthermore, PC 38:4 and PC:36:4 levels augmented in pathological conditions in in vitro AD models. BACE1 and SCD1 increases were confirmed in the hippocampus of FAD, SAD, and CADASIL.ConclusionTherefore, the findings suggest a novel convergence of BACE-1 and SCD1 in neurodegeneration, related to pro-inflammatory phospholipids.
Impact of oncoplasty in increasing breast conservation rates Post neo-adjuvant chemotherapy
Authors: Koppiker Chaitanyanand B. , Kelkar Devaki A. , Kulkarni Madhura , Kadu Shweta , Pai Mugdha , Dhar Upendra , Deshmukh Chetan , Varghese Beenu , Zamre Vaishali , Jumle Nutan , Gangurde Nutan , Joshi Anjali , Unde Rohini , Banale Rituja , Namewar Namrata , Vaid Pooja , Busheri Laleh , Thomas George , Nare Smeeta , Pereira Jerome , Badve Sunil 
Published: September 2023

IntroductionThe essential goal of neoadjuvant chemotherapy (NACT) is to downstage the primary tumor making it amenable for breast conservation surgery (BCS). However, since the safety of this surgery is paramount, post-NACT breast conservation rates remain low. As per the recommendation of the 2018 Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) overview of long-term post-NACT follow-up, we have devised a protocol for imaging, localization, rad-path analysis, and documentation of radiotherapy techniques to ensure the safety of post-NACT breast conservation.MethodsThis is a retrospective cohort of 180 breast cancer patients who received NACT and were operated on by a single surgical oncologist from 2015 to 2020. After selection based on published guidelines, patients were treated with neoadjuvant systemic (chemo or hormone) therapy. In cases where primary tumors responded and reduced to 1–2 cm in size mid-NACT, the residual tumors were localized by clips under ultrasound guidance and calcification was wire localized. All patients were treated using appropriate surgical and oncoplastic techniques where indicated. Negative margins were ensured by intra-operative rad-path analysis. Adjuvant chemotherapy and radiotherapy were given as per protocol.ResultsIn 81 cases that required mastectomy at presentation, we were able to achieve a 72.8% post-NACT BCS rate with the help of oncoplasty. Overall, 142 of 180 (80%) patients were treated with breast conserving surgery of which 80% (121 of 142) were oncoplasty. Margins were assessed on intra-operative frozen and re-excised in the same setting. No positive margins were reported in final histopath of 142 breast conservation procedures. Post-operative complication rates after breast conservation in the first year were at 17% (24 of 142 including two major complications). Patient reported outcomes were satisfactory with increased satisfaction for breast conservation compared with immediate breast reconstruction.DiscussionEmploying oncoplastic breast surgery (OBS) techniques following stringent protocols for accurate localization of the residual tumor, intra-operative rad-path analysis, and adjuvant treatments, we show successful breast conservation in 72.8% of our mastectomy-qualified patients after downstaging by NACT. We also report satisfactory outcomes for post-NACT surgery, patient-reported satisfaction, and survival.
Extracorporeal light-chain elimination in myeloma with simple medium cutoff membrane hemodialysis: a retrospective cohort study
Authors: Schaaf Christian W. , Braunisch Matthias C. , Holzmann-Littig Christopher , Pfister Frederick , Hannemann Liya , Hausinger Renate I. , Verbeek Mareike , Schmaderer Christoph , Renders Lutz , Heemann Uwe , Küchle Claudius 
Published: September 2023

BackgroundWe determined the efficacy of free light chain (FLC) removal by regular dialysis equipment (high-flux filtration) with medium cutoff (MCO) membrane hemodialysis (HD) as an adjuvant treatment to standard chemotherapy for patients with acute kidney injury complicating multiple myeloma (MM) and its impact on further dialysis dependency.MethodsSixty patients with acute dialysis-dependent renal failure secondary to MM were treated with MCO-HD (55 patients) or HCO (high cutoff)-HD (5 patients) as a control. FLC serum concentration, total protein, immunoglobulins, and LDH were measured throughout the dialysis therapy. The kidney function of the patients was followed up for 1 year.ResultsThe median age was 69 years; 25 female and 35 male patients were enrolled. HD significantly reduced FLC kappa levels in the MCO/HCO group by 58%/84% (MCO/HCO group; p &lt; 0.05) and FLC lambda by 39%/33% (MCO/HCO group; p &lt; 0.05). Single HD data (MCO) showed a relative reduction of 70% in kappa and 37% in lambda FLC concentration, as expected by the different sizes of the light chains. Renal function improved significantly and continuously from starting creatinine 5.7/3.8 mg/dl (MCO/HCO group) before HD to 1.4/2.0 mg/dl (MCO/HCO group; p &lt; 0.001) after 1 year. No significant alteration of total protein, immunoglobulins, and LDH concentrations by HD (HCO and MCO group) was observed. After 1 year, 37 of 60 patients were alive and 34 of them were off dialysis.ConclusionFLC elimination with MCO-HD is effective, technically easy, and less cost-intensive as compared with HCO-HD. Kidney function recovery in MM patients is achievable.
CEA-delta could be a biomarker of tumor phenotype, clinical stage, and chemotherapeutic response in rectal cancer with OCT4-positive cancer stem cells
Authors: Lozada-Martinez Ivan David , Bolaño-Romero Maria Paz , Lambis-Anaya Lina , Liscano Yamil , Suarez-Causado Amileth 
Published: September 2023

BackgroundThere is very limited evidence on biomarkers for evaluating the clinical behavior and therapeutic response in rectal cancer (RC) with positive expression of cancer stem cells (CSCs).MethodsAn exploratory prospective study was conducted, which included fresh samples of tumor tissue from 109 patients diagnosed with primary RC. Sociodemographic, pathological and clinical characteristics were collected from medical records and survey. The OCT4 protein was isolated using the Western Blot technique. It was calculated the ΔCEA, ΔOCT4, and ΔOCT4/GUSB values by assessing the changes before and after chemotherapy, aiming to evaluate the therapeutic response.ResultsPatients had an average age of 69.9 years, with 55% (n=60) being male. Approximately 63.3% of the tumors were undifferentiated, and the most frequent staging classification was pathological stage III (n=64; 58.7%). Initial positive expression was observed in 77.1% of the patients (n=84), and the median ΔCEA was -1.03 (-3.82 - 0.84) ng/ml, with elevated levels (&lt; -0.94 ng/ml) found in 51.4% of the subjects (n=56). Being OCT4 positive and having an elevated ΔCEA value were significantly associated with undifferentiated tumor phenotype (p=0.002), advanced tumor progression stage (p &lt;0.001), and negative values of ΔOCT4 (p &lt;0.001) (suggestive of poor therapeutic response) compared to those without this status.ConclusionThis study identified a significant and directly proportional association among the values of ΔCEA, ΔOCT4, and ΔOCT4/GUSB. These findings suggest that ΔCEA holds potential as a clinical biomarker for determining the undifferentiated tumor phenotype, advanced clinical stage, and poor therapeutic response in RC with CSCs positive expression.